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^LECTURES 

ON 

AUTO- INTOXICATION  IN  DISEASE? 

OR 

SELF-POISONING  OF  THE  INDIVIDUAL 


CH.  BOUCHARD, 


PROFESSOR  or  PATHOLOGY  AND  THERAPEUTICS,  MEMBER  or  THE  ACADEMY  OF  MEDICINE, 
AND  PHYSICIAN  TO  THE  HOSPITALS,  PARIS. 


TRANSLATED,  WITH  A  PREFACE, 


THOMAS  OLIVER,  M.A.,  M.D.,  F.R.C.P., 

PROFESSOR  OF  PHYSIOLOGY,  UNIVERSITY  or  DURHAM  ;  PHYSICIAN  TO  THE  ROYAL  INFIRMARY,  NEWCASTLE- 

nPON-TYNE  ;   AND  EXAMINER  IN  PHYSIOLOGY,  CONJOINT  BOARD  OF  ENGLAND. 


PHILADELPHIA  : 
THE  F.  A.  DAVIS  COMPANY. 

LONDON : 

F.  J.  REBMAN. 

1894. 


COPYRIGHT,  1894. 

THE  F.  A.  DAVIS  COMPANY. 
[Registered  at  Stationers'  Hall,  London,  England.] 


Philadelphia,  Pa.,  U.S.A.: 

The  Medical  Bulletin  Printing  House, 

1916  Cherry  Street. 


13 
8 


PREFACE. 


IN  placing  this  translation  of  Professor  Bouchard's  "  Lectures 
on  Auto-Intoxication  in  Disease"  before  my  medical  brethren, 
I  feel  that  I  am  performing  a  service  highly  useful  to  the  pro- 
fession. No  apology  is  required  from  me,  unless  it  be  for  the 
failures  on  my  part  to  render  fluently  into  English  the  meaning 
of  the  French  text.  I  have  tried,  as  far  as  possible,  to  give  a 
literal  and  a  readable  translation. 

Bouchard  deals,  in  his  "  Auto-Intoxication,"  with  subjects 
of  every -day  interest  to  the  medical  practitioner.  Man}'  of  the 
facts  therein  alluded  to  can  no  longer  be  ignored.  Putrefactive 
processes  in  the  intestinal  canal  and  the  development  of  phj-si- 
ological  and  pathological  alkaloids  play  an  important  part  in 
many  diseased  processes  until  latelj7  unknown  or  misunder- 
stood. These  lectures  may,  therefore,  be  regarded  as  an  inquiry 
into  the  operation  of  poisons  introduced  from  without  or  gen- 
erated within  the  body  of  man,  and  the  part  they  play  in  health 
and  disease.  No  subject  commands  a  greater  interest;  none 
demands  more  serious  study. 

Death  frequently  carries  off  in  a  few  hours  or  days  individuals 
who  are  in  the  prime  of  life  and  in  apparent  good  health,  and  at 
whose  post-mortem  the  most  careful  examination  fails  to  reveal 
alterations  of  structure  such  as  can  explain  the  fatal  stroke. 
Epidemics,  not  of  a  specific  character,  but  traceable  to  poisoned 
water  or  food,  have  unexpectedly  appeared  in  certain  neighbor- 
hoods ;  or  members  of  a  marriage  party  have  died  without  much 
warning,  death  being  attributed,  and  very  properly,  to  some 
article  of  diet  partaken  of  at  the  wedding-feast.  These  are  the 
cases  that  have  aroused  public  opinion  and  awakened  profes- 
sional interest  in  a  subject  toward  the  elucidation  of  which  the 
pathological  chemist  has  vied  with  the  bacteriologist. 

The  investigations  of  Selmi,  Brieger,  Pasteur,  Frankel,  Han- 
kin,  Martin,  and  Bouchard,  not  to  mention  others,  have  shown 
how  disease  may  depend  upon  the  presence  in  the  system  of  sub- 

(v) 

;      /  ' 


yi  PREFACE. 

stances  capable  of  combining  with  acids  to  form  chemical  salts, 
and  which  correspond  to  inorganic  and  vegetable  bases.  It 
was  to  these  substances  that  the  Italian  toxicologist,  Selmi,  gave 
the  name  of  ptomaines, — by  which  is  meant  chemical  compounds 
basic  in  character,  and  formed  by  the  action  of  bacteria  upon 
organic  matter.  It  is  owing  to  these  basic  properties  and  their 
resemblance  to  vegetable  alkaloids  that  ptomaines  are  sometimes 
spoken  of  as  putrefactive  or  vegetable  alkaloids, — the  term  leuco- 
maines,  or  animal  alkaloids,  being  reserved  for  those  basic  sub- 
stances resulting  from  tissue  metabolism  in  the  body. 

Without  discussing  the  question  as  to  whether  ptomaines 
are  poisonous  or  not, — for  Bouchard  in  these  pages  confines  him- 
self rather  to  the  general  action  of  animal  poisons  than  to  a 
designation  of  them, — it  is  sufficient  to  state  that  all  ptomaines 
are  not  poisonous.  Some  are  quite  inert.  Brieger  restricts  the 
term  ptomaine  to  the  non-poisonous  basic  products,  whilst  those 
that  are  poisonous  he  calls  "  toxins."  Ptomaines  contain 
nitrogen,  and  in  this  respect  they  resemble  vegetable  alkaloids. 
Many  of  them  contain  oxygen,  whilst  in  others  this  is  awanting. 

The  one  invariable  circumstance  surrounding  the  development 
of  ptomaines  is  the  part  played  by  bacteria.  As  ptomaines  owe 
their  development  to  the  activity  of  micro-organisms  it  must 
follow  that  the  alkaloid  formed  will  depend  upon  the  peculiar  bac- 
terium present,  the  nature  of  the  material  acted  upon,  the  con- 
ditions under  which  putrefaction  goes  on,  and  probably,  too,  upon 
the  health  of  the  individual  in  whose  body  the  putrefactive  proc- 
esses are  taking  place.  It  has  frequently  been  demonstrated  how 
the  nature  of  the  soil  alters  the  character  of  the  micro-organisms 
that  have  flourished  upon  it.  Temperature  exercises  its  own  pecu- 
liar influence.  Some  bacteria,  too,  require  oxygen,  whilst  others 
are  capable  of  thriving  apart  from  it.  Thus  it  was  that  Pasteur 
divided  bacteria  into  two  classes, — the  aerobic  and  the  anaerobic. 
When  putrefaction  occurs  in  the  presence  of  air,  the  ptomaines 
formed  naturally  differ  from  those  produced  under  conditions 
from  which  air  is  largely  excluded.  At  all  times  they  are  ex- 
tremely subtle.  Occurring  as  transition  products  in  the  proc- 
esses of  putrefaction,  ptomaines  are  to  be  regarded  as  "  tem- 
porary forms  through  which  matter  passes  while  it  is  being 


PREFACE.  vii 

transformed  by  the  activity  of  bacteria  from  the  organic  to  the 
inorganic  state  "  (Vaughan  and  Novy,  "  Ptomaines  and  Leuco- 
maines").  The  daily  round  of  human  life  is  a  repetition  of  in- 
tegrations and  disintegrations,  of  processes  of  building  up  and 
breaking  down.  Metabolism  is  taking  place  everywhere  within 
the  human  body,  with  the  result  that  the  complex  molecules  of 
brain  and- muscle  in  their  catalysis  pass  through  intermediate 
stages,  and  are  finally  resolved  into  carbonic  acid,  water,  and  am- 
monia. We  do  not  know  what  part  oxygen  plays  in  putrefaction, 
but  the  researches  of  Pasteur  have  shown  how  important  is  the 
role  pkiyed  by  myriads  of  micro-organisms.  We  are  forced  to 
acknowledge  the  great  impetus  given  to  disintegrating  processes 
in  organic  matter  by  bacteria.  In  no  part  of  the  body  is  this 
more  true  than  in  the  intestine.  At  the  present  time  it  is  a 
debatable  question  as  to  how  far  even  normal  digestion  may 
not  be  aided  by  the  multiplication  of  micro-organisms.  Pas- 
teur has  isolated  as  many  as  seventeen  microbes  in  the  mouth. 
Some  of  these  dissolve  albumen,  gluten,  and  casein,  whilst  others 
are  capable  of  converting  starch  into  glucose.  Considering  the 
multiform  changes  that  take  place  in  the  small  intestine  during 
digestion, — changes  of  a  chemical,  putrefactive,  and  fermentative 
nature, — there  must  be  produced  substances  of  a  highly  complex 
nature — alkaloids  or  ptomaines — which,  when  absorbed  into  the 
S}rstem,  may  seriously  affect  the  vitality  of  the  individual.  We 
are  all,  to  some  extent,  protected  against  the  injurious  effects  of 
micro-organisms  by  the  fact  that  the  products  secreted  as  the 
result  of  microbal  activity  react  upon  the  organisms  themselves, 
and  thus  limit  their  longevity. 

It  is  the  function  of  the  gastro-intestinal  juices,  aided  by  the 
movements  of  the  stomach  and  intestine,  to  convert  foods  into 
such  soluble  forms  that  they  can  be  utilized  by  the  econom}'. 
Landois  and  Stirling  show  how  undigested  proteids  and  their 
derivatives  may  be  acted  upon  by  fungi.  "  Many  fission  fungi — 
e.g.,  bacillus  subtilis  and  the  spirillum  of  cheese — can  produce  a 
peptonizing  ferment ;  so  that  a  small  amount  of  the  peptonizing 
done  in  the  intestine  may  be  due  to  microbes."  This,  though 
not  proved,  has  been  rendered  probable  by  the  experiments  of 
Vignal.  "From  the  normal  intestinal  mucus  Babes  has  isolated 


Viii  PREFACE. 

five  species  of  bacteria,  whilst  an  enormous  number  of  micro- 
organisms exist  in  the  large  intestine  and  faeces.  All  these 
organisms  resist  the  action  of  the  digestive  fluids,  save  a  few, 
which  are  dissolved  by  the  gastric  juice.  The  researches  of 
Duclaux,  Vignal,  and  others  have  shown  that  certain  of  these 
micro-organisms  secrete  soluble  ferments  identical  in  their  action 
with  the  ferments  of  the  digestive  juices.  Vignal  states  that  cer- 
tain of  these  organisms  contribute  to  the  dissolution  of  food  in  the 
intestine.  It  is  certain  that  they  contribute  to  many  processes 
of  fermentation  and  decomposition  which  go  on  in  the  intestine. 
During  fcetal  life  these  organisms  are  wanting,  but  they  are 
numerous  a  few  days  after  birth.  In  this  connection  we  cannot 
fail  to  remember  that  bacteria  by  their  action  can  produce  in  albu- 
minous fluids  albumoses  and  peptones,  and  that  the  former  bodies 
are  now  regarded  by  bacteriologists  as  substances  which  play  an 
important  role  in  many  pathological  processes  "  (Landois  and 
Stirling,  "  Physiology,"  page  344). 

Bouchard,  in  his  "Auto-Intoxication,"  clearly  indicates  to  us 
that  man  is  constantly  standing,  as  it  were,  on  the  brink  of  a 
precipice  ;  he  is  continually  on  the  threshold  of  disease.  Every 
moment  of  his  life  he  runs  the  risk  of  being  overpowered  by 
poisons  generated  within  his  system.  Self-poisoning  is  only 
prevented  by  the  activity  of  his  excretory  organs,  chiefly  the 
kidney,  and  by  the  watchfulness  of  the  liver,  which  acts  the  part 
of  a  sentinel  to  the  materials  brought  to  it  by  the  portal  vein 
from  the  alimentary  canal.  Disease  is  not  something  altogether 
apart  from  the  individual.  The  patient  and  his  disease  are  too 
often  found  living  under  identical  conditions. 

Lauder  Brunton,  in  his  "  Introduction  to  Modern  Thera- 
peutics," devotes  considerable  space  to  the  discussion  of  this 
all-important  subject.  Chemical  investigation  has  shown  how 
disease  depends  upon  the  products  of  putrefaction  and  fermen- 
tation, rather  than  upon  the  direct  action  of  the  microbes  upon 
the  tissues.  It  is  this  fact  which  renders  knowledge  of  the  life- 
history  of  bacteria  so  valuable  to  us ;  for,  long  after  the  microbes 
have  been  destroyed  the  enzymes,  or  ferments,  which  they  formed 
continue  to  act,  and  are  not  destroyed  by  a  temperature  which  is 
destructive  to  the  organisms  themselves. 


PREFACE.  IX 

Scarcely  a  month  passes  without  a  death  being  reported  and 
traceable  to  a  meal  of  tainted  meat.  Dr.  Stevenson,  of  Guy's 
Hospital,  has  recently  demonstrated  the  far-reaching  and  fatal 
consequences  of  such  a  diet.  I  myself  have  reported  lately  in 
the  Lancet  a  case  of  acute  peripheral  neuritis,  ending  in  rapid 
death,  and  due  in  all  probability  to  certain  viands  partaken  of 
at  a  particular  banquet.  The  cooking  of  meat,  already  tainted 
by  the  presence  of  microbes,  whilst  it  is  destructive  to  the  organ- 
isms, still  allows  the  ferments  they  have  formed  to  carrj-on  their 
work  of  decomposition.  It  is  thus  that  the  cold  meat  or  beef- 
steak pie  which  forms  the  material  substratum  of  the  Monday's 
dinner,  though  eaten  with  impunity  when  hot  on  the  previous 
day,  becomes  a  source  of  danger.  Of  this  I  had  a  striking  illus- 
tration a  few  years  ago,  in  the  industrial  schools  of  this  city,  of 
which  I  happen  to  be  the  honorary  physician.  A  certain  Sim- 
day's  dinner  of  roast  beef  had  been  enjoyed  by  all  the  inmates 
of  the  school.  On  the  following  Tuesday  morning  there  was 
an  epidemic  of  diarrhoea  in  the  school  such  as  had  never  been 
witnessed  before,  there  being  upward  of  one  hundred  cases. 
Several  of  the  older  lads  were  not  slow  to  express  the  opinion 
that  their  food  had  been  drugged  by  materials  taken  from 
the  surgery.  The  case,  however,  was  perfectly  clear.  Those 
children  who  had  not  partaken  of  the  slightly  warmed-up  cold 
meat  left  over  from  the  Sunday's  dinner — although  placed  under 
the  same  dietetic  conditions,  except  as  regards  that  one  par- 
ticular meal — alone  escaped.  It  is  to  subjects  such  as  these 
that  Bouchard  draws  special  attention,  and  shows  the  efficacy  of 
intestinal  antisepsis. 

Setting  aside  the  chapters  on  the  "  Toxicity  of  Urines,"  and 
in  which  Professor  Bouchard  is,  perhaps,  seen  to  greatest  advan- 
tage, the  lectures  devoted  to  typhoid  fever  and  cholera  contain 
suggestions  of  considerable  value  from  a  therapeutic  point  of 
view.  It  is  only  lately  we  have  come  to  recognize  that,  once  the 
dangers  incidental  to  typhoid  fever  have  been  successfully  over- 
come, there  are  risks  yet  to  be  met ;  in  a  word,  auto-intoxication 
from  poisons  generated  within  the  intestinal  canal.  There  are 
few  medical  men  who  have  not  had  some  experience  of  the  suc- 
cess which  has  followed  the  administration  of  intestinal  anti- 


X  PREFACE. 

septics  in  enteric  fever.  In  my  own  consulting  practice  I  have 
used  beta-naphthol  with  excellent  results.  I  can  recall  one  case 
in  particular,  where  a  young  gentleman,  in  the  fifth  week  of  en- 
teric fever,  was  so  prostrated  and  blanched  by  intestinal  dis- 
charges that  he  could  not  be  turned  in  bed  without  fainting,  with 
an  almost  imperceptible  pulse,  a  temperature  of  105°  to  106°  F., 
almost  in  extremis,  and  whose  life  I  consider  was  saved  by  beta- 
naphthol  and  other  intestinal  antiseptics.  We  know  that  naph- 
thalin  is  sparingly  soluble,  and  that  it  passes  to  a  large  extent 
unchanged  through  the  alimentary  canal.  No  one  denies  to  it, 
however,  the  power  of  destroying  the  disagreeable  odor  of  the 
motions.  Salol,  or  the  salicylate  of  phenol,  has  also  given  ex- 
cellent results.  Having  passed  through  the  stomach  undecom- 
posed,  it  comes  into  contact  with  the  pancreatic  juice  in  the 
duodenum,  and  is  thereby  split  up  into  salicylic  and  carbolic 
acids.  The  latter  is  set  free  where  it  is  required,  but,  as  Brunton 
says,  it  has  the  disadvantage  of  being  poisonous,  and  so  betol  or 
salicylate  of  beta-naphthol  is  to  be  recommended  instead.  All 
the  substances  belonging  to  the  phenol  class  may  be  regarded  as 
antiseptics  in  the  largest  sense  of  the  word.  Outside  the  system 
they  readily  arrest  the  development  of  germs,  but  within  it  their 
action  is  not  so  definite.  They  are  antiseptics  so  long  as  they 
are  not  absorbed.  Once  this  occurs,  the  antiseptic  power  of 
the  phenols  is  suspended.  They  then  form  non-antiseptic  com- 
pounds, Hoelscher  in  his  experiments  having  shown  that  the 
blood  does  not  become  sterile  even  after  large  doses  of  guaiacol. 
A  fairly  large  experience  of  the  treatment  of  cei'tain  diseases 
in  which  the  blood  is  poisoned — e.g.,  puerperal  fever,  certain 
forms  of  pneumonia,  ulcerative  endocarditis,  etc. — has  led  me  to 
place  considerable  reliance  upon  the  efficacy  of  the  phenols. 
When  absorbed  they  no  longer  exercise  a  direct  action  upon  the 
germs,  but  they  exert  another  action,  viz.,  a  de-poisoning  one. 
Seifert  and  Hoelscher  maintain  that  when  the  phenols  are  ab- 
sorbed they  induce  a  de-poisoning  of  the  bod}-  by  combining 
with  and  eliminating  the  toxic  albumens  produced  by  the  action 
of  disease  germs.  Phenols  are  not  found  free  in  the  blood. 
They  are  eliminated  in  the  urine  as  ethereal  sulphates,  in  the 
form  of  salts  that  have  resulted  from  the  oxidation  of  some  com- 


pound  of  the  phenols  with  albumen,  and,  to  a  large  extent,  with 
toxic  albumens,  the  result  of  the  vital  activity  of  germs.  It  is 
believed  that  the  compounds  of  toxic  albumens  and  phenols 
are  non-toxic.  The}7  quickly  undergo  oxidation,  hence  the  ap- 
pearance of  phenols  in  the  urine  as  ethereal  sulphates.  Chemical 
disintegration  and  recombinations  undoubtedly  occur,  and  to 
these  must  be  attributed,  by  the  process  of  de-poisoning  just 
alluded  to,  the  good  results  that  follow  the  administration  of 
antiseptics  in  certain  forms  of  blood-poisoning.  Under  all  cir- 
cumstances a  rigid  intestinal  antisepsis  cannot  but  be  of  the 
greatest  possible  utility. 

The  salols  pass  through  the  stomach  without  undergoing 
decomposition.  In  the  small  intestine  salols  and  phenols  are 
split  up  into  their  antiseptic  constituents :  salol  into  salicylic  and 
carbolic  acid,  betol  into  salicylic  acid  and  beta-naphthol,  whilst 
guaiacol  carbonate — the  new  remedy  for  phthisis — decomposes 
into  guaiacol  and  carbonic  acid. 

I  shall  leave  the  reader  to  follow  Dr.  Bouchard  in  his  criti- 
cism of  cholera  and  its  relation  to  the  comma  bacillus. 

The  part  played  by  auto-intoxication  in  mental  diseases  is 
attracting  attention.  In  the  Medical  Week,  August  11,  1893, 
there  is  a  length}-  report  upon  the  subject  as  discussed,  at  the 
French  Congress  of  Psychological  Medicine,  by  Drs.  Re'gis, 
Chevalier-Lavaure,  and  others.  It  has  long  been  known  that  the 
various  fluids  of  the  body  undergo  modifications  in  the  insane. 
Recent  investigation  has  shown  that  the  urine  is  much  less  toxic 
than  normal  in  cases  of  mania,  while  the  lethal  action  of  this 
fluid  is  increased  in  melancholia.  Maniacal  urine  gives  rise  to 
excitement  and  convulsions  when  injected  into  an  animal,  while 
the  injection  of  urine  from  a  case  of  melancholia  is  followed  by 
depression  of  spirits,  restlessness,  and  stupor, — a  proof  that 
auto-intoxication  is  the  cause  and  not  the  effect  of  the  mental 
condition.  Besides,  in  the  mental  disorders  that  arise  during 
the  course  of  such  infectious  diseases  as  typhoid  and  other 
eruptive  fevers,  as  well  as  in  puerperal  fever,  there  is  little  doubt 
that  these  disturbances  are  due  to  the  action  of  pathogenic 
organisms,  either  directly  or  indirectly  through  the  influence  of 
their  toxins ;  and  according  to  the  stage  of  the  illness,  so  is  the 


xii  PREFACE. 

character  of  the  mental  symptoms.  One  has  only  to  mention 
these  facts  to  throw  into  bold  relief  the  excellent  results  that 
frequently  follow  the  administration  of  antiseptics  and  excitants 
to  the  emunctories. 

This  translation  is  given  in  the  hope  that  English  readers 
may  find  in  its  pages  much  that  is  interesting  from  a  pathological 
point  of  view,  and  much  that  is  valuable  and  suggestive  from  a 
therapeutical.  For  mistakes  attributable  to  myself  I  crave  in- 
dulgence ;  for  Americanisms  in  spelling  I  am  in  no  way  respon- 
sible. As  a  translation,  I  am  only  too  conscious  that  the  work 
is  far  from  being  perfect.  If,  however,  the  book  serves  a  useful 
end,  I  shall  be  fully  repaid  for  the  time  and  labor  I  have  spent 
upon  it. 

I  cannot  draw  this  preface  to  a  close  without  thanking  Pro- 
fessor Bouchard  for  the  freedom  he  has  allowed  me  in  translating 
and  publishing  this  work,  and  also  of  expressing  my  sense  of 
indebtedness  to  my  friend  and  clinical  clerk,  Mr.  Wm.  Turnbull, 
for  his  kindness  in  revising  the  proofs,  and  for  the  great  help  he 
has  afforded  me  in  drawing  out  the  index. 

THOMAS  OLIVER. 

7  ELLISON  PLACE,  NEWCASTLK-UPON-TYNK, 
January,  1894. 


CONTENTS. 


LECTURE  I. 

PATHOGENIC   PROCESSES   IN    THE    MAIN, 1 

LECTURE  II. 

PRODUCTION   AND    ELIMINATION    OF   POISONS  BY   THE    ORGANISM,       14 

LECTURE  III. 

PRELIMINARIES    TO    THE    EXPERIMENTAL    STUDY    OF    THE    TOX- 

ICITY   OF   THE   PRODUCTS   OF   EMUNCTION,      .  .  .  .22 

LECTURE  IV. 

ON    THE   TOXICITY   OF   URINES, 29 

LECTURE  V. 

CAUSES  OF   THE   TOXICITY   OF   URINE, 46 

LECTURE  VI. 

TOXIC    PRINCIPLES    IN    URINE — THE    PART    THEY   PLAY   IN  PRO- 
DUCING  UREMIA, 60 

LECTURE  VII. 

ORIGIN    OF    THE    TOXIC     SUBSTANCES     OF     URINE— TOXICITY    OF 

THE   BLOOD   AND   TISSUES, 69 

LECTURE  VIII. 

ORIGIN    OF    THE    TOXIC     SUBSTANCES     OF     URINE — TOXICITY    OF 

THE  FLUIDS  AND  OF  THE  CONTENTS  OF  THE  INTESTINE 
(BILE  AND  THE  PRODUCTS  OF  PUTREFACTION),  .    .    .  83 

(xiii) 


XIV  CONTENTS. 

LECTURE  IX. 

ORIGIN    OF    THE    TOXIC     SUBSTANCES    OF    URINE — TOXICITY    OF 

THE   PRODUCTS   OF   PUTREFACTION   AND   OF   THE   F.&CES,       .         90 

LECTURE  X. 

INTESTINAL   ANTISEPSIS, 97 

LECTURE  XI. 

PATHOGENESIS  OF  UREMIA — DISTINCTION  BETWEEN  THE  SYMP- 
TOMS OF  THE  PRE-UR^EMIC  PERIOD  OF  NEPHRITIS  AND  THE 
SYMPTOMS  OF  INTOXICATION,  .  .  .  .  .  .102 

LECTURE  XII. 

PATHOGENESIS     OF    UREMIA — DISCUSSION    OF    THE     EXCLUSIVE 

THEORIES, 108 

LECTURE  XIII. 

PATHOGENESIS     OF    UREMIA — DISCUSSION    OF     THE    EXCLUSIVE 

THEORIES, 114 

LECTURE  XIV. 

PATHOGENESIS  OF  UREMIA— THE  PART  PLAYED  BY  ORGANIC 
SUBSTANCES  AND  MINERAL  MATTERS  IN  UR^EMIC  INTOXI- 
CATION,   120 

LECTURE  XV. 

THE   THERAPEUTIC   PATHOGENESIS   OF   URAEMIA,  .  .  .      127 

LECTURE  XVI. 

TRANSITORY    OR     ACUTE     AUTO-INTOXICATION    OF     INTESTINAL 

ORIGIN — INTERNAL  STRANGULATION  AND  CONSTIPATION,      .       138 

LECTURE  XVII. 

ACUTE  OR  TRANSITORY  INTESTINAL  AUTO-INTOXICATION — GAS- 
TRIC DISORDERS INDIGESTION — POISONING  BY  TAINTED 

MEATS,     ...  .146 


CONTENTS.  XV 

LECTURE  XVIII. 

CHRONIC     GASTRO-INTESTINAL     AUTO-INTOXICATIONS  —  DILATA- 
TION  OP   THE   STOMACH, 154 

LECTURE  XIX. 

DILATATION   OF   THE    STOMACH — ETIOLOGY,  PATHOGENESIS,   AND 

THERAPEUSIS, 173 

LECTURE  XX. 

AUTO-INTOXICATION  OF  INTESTINAL  ORIGIN — TYPHOID  FEVER,     .       187 

LECTURE  XXI. 

PATHOGENIC   THERAPEUSIS   OF   TYPHOID   FEVER — ANTISEPSIS   OF 

THE   INTERNAL   MEDIUM, 194 

LECTURE  XXII. 

ON  THE  PATHOGENIC  THERAPEUTICS  OF  TYPHOID  FEVER — THE 

TREATMENT  OF  HIGH  TEMPERATURE,    ....   201 

LECTURE  XXIII. 

PATHOGENIC   THERAPEUTICS   OF  TYPHOID  FEVER — NEW  MODE   OF 

BATHING   IN    FEVERS;    DIETING   OF   FEVER   PATIENTS,  .      208 

LECTURE  XXIV. 

AUTO-INTOXICATION   BY   BILE.      PATHOGENESIS   OF  JAUNDICE,     .      222 

LECTURE  XXV. 

MALIGNANT   JAUNDICE  :    AGGRAVATED  JAUNDICE,       .  .  .      229 

LECTURE  XXVI. 

THE   TOXIC    NATURE   OF  PATHOLOGICAL   URINES,         .  .  .      236 

LECTURE  XXVII. 
PYOCYANIC  DISEASE,     POISONING;  ACCIDENTS  IN  DIABETES,      .     243 


Xvi  CONTENTS. 

LECTURE  XXVIII. 
POISONING  BY   PATHOLOGICAL   POISONS.       CHOLERA,  .  .  .249 

LECTURE  XXIX. 
CHOLERA  (CONTINUED), 257 

LECTURE  XXX. 
CHOLERA  (CONCLUSION), 265 

LECTURE  XXXI. 

THE   GENERAL   TEIERAPEUTICS   OF   SELF-POISONING,     .  .  .       273 

LECTURE  XXXII. 
GENERAL  RECAPITULATION, 280 

INDEX,    ,  289 


LECTURES  ON  AUTO-INTOXICATION. 


LECTURE  I. 
PATHOGENIC  PROCESSES  IN  THE  MAIN. 

Preponderance  of  pathogenesis  iu  the  preoccupations  of  contemporary  medicine. 
The  four  great  pathogenic  processes :  primary  elementary  dystrophies  ;  nerve 
reactions ;  previous  disturbances  of  nutrition ;  infection.  Influence  of 
earlier  disturbances  of  nutrition  upon  the  production  of  most  of  the  chronic 
and  of  many  acute  diseases.  Definition  of  diathesis  considered  as  a  morbid 

temperament. Infection.      Living  nature  of  contagious  matter.     Small 

number  of  diseases  for  which  parasiticism  has  been  established  with  certainty. 
Extreme  probability  of  the  hypothesis  according  to  which  all  contagion 
might  be  the  function  of  a  vegetable  organism.  The  part  which  medicine 
plays  in  the  presence  of  the  doctrine  of  micro-organisms.  The  abundance  of 
microbes  around  man  and  the  relative  infrequency  of  infection.  Association 
and  combination  of  pathogenic  processes.  The  powerlessness,  as  a  rule,  of 
nervous  reactions  to  determine  by  them  alone  disease. Morbid  predis- 
positions established  by  the  arthritic  and  scrofulous  diatheses.  Disease 
opportunity.  Diathesis  of  short  duration  established  by  a  nervous  reaction, 
which  interferes  for  the  time  being  with  nutrition,  and  opens  the  portal  to 
Infection.  Diathesis  acquired.  Diathesis  hereditary.  Interrupted  accidents 

in  the  course  of  diatheses. Bond  between  new  discoveries  and  traditional 

medical  observation.     The  physician  has  a  double  duty :  to  contend  with 

microbes,  and  to  fortify  the  organism  against  them. How  disturbance 

of  nutrition  may  produce  disease.  Intoxication  of  the  organism  by  in- 
crease or  retention  of  normal  matter.  Intoxication  by  the  formation  of 

abnormal  matter. The  part  intoxication  plays  iu  the  processes  of  infection. 

Five  hypotheses  relative  to  the  mode  of  action  of  pathogenic  microbes.  The 
role  of  microbes  iu  the  formation  of  certain  poisons  normal  to  the  organism. 

GENERAL  PATHOLOGY. 

WE  are  living  in  an  age  when  it  is  proper  to  live  and  when 
all  are  interested  in  medical  matters.  It  is  not  that  medicine 
has,  in  ai^  sense  of  the  word,  revived,  but  that  she  has  simply 
changed  her  attitude  of  observation. 

After  having  devoted  herself  during  many  long  }-ears  to  the 
verification  of  symptoms,  to  the  research  of  anatomical  lesions, 
to  the  study  of  pathological  physiology,  she  comes  at  last  to 
study  the  origin  of  disease.  What  is  characteristic  of  these 
modern  days,  so  far  as  medicine  is  concerned,  is  the  high  place 
we  assign  to  the  study  of  the  origin  of  diseases. 

1  0) 


2  LECTURES   ON    AUTO-INTOXICATION. 

If  the  causes  are  innumerable,  you  know  that  the  processes 
following  those  which  induce  disease  can  be  relegated  to  four 
types.  These  four  chief  pathogenic  processes  are:  (1)  primary 
elementary  dystrophies,  (2)  nerve  reactions,  (3)  disturbances 
antecedent  to  nutrition,  and  (4)  infection. 

The  first  of  these  processes  is  the  most  simple,  but  it  is  the 
least  studied,  and  I  may  add  that  it  is  almost  completely  un- 
known. It  is  that  which  arises  from  the  vital  activity  of  cells, 
when  it  is  directly  brought  under  our  notice  by  some  cause, 
physical,  mechanical,  or  chemical;  from  the  lightning-stroke  to 
the  intoxications,  or  by  the  way  of  trauinatism.  If  one  neglects 
more  than  is  necessary  the  study  of  that  simple  process,  it  is  be- 
cause very  often  it  is  complicated  with  effects  of  a  local  char- 
acter, vascular  or  otherwise,  which  are  the  reflex  result  of  ner- 
vous requirements. 

We  have  known  for  a  very  long  time  the  important  part 
played  by  the  nervous  system  as  an  intermediary  in  the  produc- 
tion of  disease.  Have  we  exaggerated  it,  or  have  we  accorded 
to  the  reflexes  a  pathogenic  influence  greater  than  that  which 
they  have  in  reality  ?  When  they  are  set  in  operation  in  a  per- 
son in  good  health  they  only  rarely  cause  the  development 
of  the  malady  properly  called ;  their  role  is  often  to  bring 
about  fleeting  indispositions  or  troubles,  for  a  longer  or  shorter 
period,  to  the  extent  of  realizing  predisposition  or  the  morbid 
opportunity. 

You  know  that  those  pathogenic  influences  are  peripheral  or 
central.  It  is  in  their  action  upon  the  cutaneous  nerve-endings 
that  cold  and  moisture  interpose  as  a  cause  of  disease  ;  it  is  by 
their  direct  action  upon  nerve-centres  that  disorders  of  the  af- 
fections, changes  of  disposition,  mental  fatigue,  and  so  many 
other  psychical  disturbances  frequently  bring  about  deteriorated 
health.  Generally  speaking,  it  is  only  a  condition  accessory  or 
predisposing  to  the  development  of  the  disease ;  it  is  rarely  the 
nearest  or  exclusive  provocative  cause. 

The  two  other  pathogenic  processes  of  chief  importance  are 
disturbances  antecedent  to  nutrition  and  infection.  Disturb- 
ances of  nutrition  rule,  in  my  opinion,  the  largest  number  of 
chronic  diseases,  and  explain  the  appearance  of  many  illnesses 


PATHOGENIC    PROCESSES    IN    THE    MAIN.  3 

of  an  acute  character.  I  had  devoted  to  this  study  the  first 
years  of  my  profession,  and  I  have  returned  to  it  when  I 
have  tried  to  determine  the  exact  domain  of  diathesis  and  the 
processes  by  which  we  can  undertake  the  cure  of  diathetic  dis- 
eases. My  constant  effort  has  been,  and  my  duty  will,  perhaps, 
be,  to  render  to  diatheses  the  part  which  is  theirs  by  right  in 
the  prejudices  of  medicine.  To  do  that,  I  have  been  obliged  to 
disengage  them  from  the  mystic  cloud  which  encircled  them,  and 
I  have  rendered  them  physiologically  intelligible  when  I  have 
said  that  diathesis  is  a  permanent  disturbance  of  nutrition,  which 
prepares,  provokes,  and  maintains  different  diseases,  as  seen  in 
their  location,  their  evolution,  and  pathological  process.  This 
was  to  restore  to  diathesis  its  traditional  signification  ;  it  was  to 
consider  it  anew  as  a  morbid  temperament. 

Infection  is  the  last  of  the  four  pathogenic  processes.  We 
find,  again,  traces  of  this  notion  very  far  back  in  the  past,  but  it 
has  assumed  form  only  within  the  last  quarter  of  this  century. 
It  is  what  we  call,  or  it  is  what,  now  particularly,  deserves  to  be 
called,  contagium  vivum. 

The  interpretation  of  infection  has  provoked  the  warmest 
discussions  in  our  times.  The  brilliancy  of  certain  recent  dis- 
coveries has  been  to  fascinate  and  to  dazzle.  It  has  caused, 
according  to  temperament,  enthusiasm  or  sarcasm,  infatuation 
or  dread.  Infatuation  or  dread, — these  are  two  sentiments 
which  science  repudiates.  She  will  continue,  in  spite  of  resist- 
ance, and  in  spite  of  the  intemperate  displays  of  an  exaggerated 
enthusiasm,  to  march,  serenely  and  unmoved,  toward  truth. 

At  the  present  time  the  living  nature  of  contagious  material 
is  beyond  all  question.  Ever  since  man  has  known  contagion 
he  has  been  asking  himself  of  what  it  might  consist.  Of  all 
hypotheses,  not  one  has  been  verified,  until  the  day  in  which  it 
has  been  demonstrated  that  in  the  body  of  an  individual  attacked 
by  a  contagious  disease  there  exist  the  lower  vegetable  organ- 
isms, capable  of  implanting  themselves  and  of  multiplying  in 
the  tissues  of  a  healthy  man,  and  of  determining  in  him  a  disease 
similar  to  the  original.  That  is  the  final  termination  of  all  sys- 
tems relative  to  contagion. 

Demonstration  1ms  not  been  made  for  all  contagious  diseases; 


4  LECTURES   ON   AUTO-INTOXICATION. 

doubtless  it  is  not  even  complete,  save  in  a  number  more 
limited  than  we  maintain.  Parasiticism  is  established  with 
absolute  certainty  in  four  diseases  of  man, — charbon,  glanders, 
tuberculosis,  and  gaseous  gangrene  ;  besides,  proof  is  nearly 
established  in  blennorrhagia  and  erysipelas.  To  these  diseases  of 
men  we  may  add  several  experimental  septicaemias, — the  cholera 
of  fowls,  swine  fever,  and  symptomatic  pustule.  This  is  a  small 
number,  and  yet  it  is  large  if  we  consider  that  in  those  cases 
alone  where  infection  could  be  interpreted  in  a  positive  manner 
the  solution  has  been  universally  agreed  upon.  Contagion  has 
always  been  recognized  as  the  function  of  a  vegetable  organism. 

Have  we  the  right  to  generalize,  and  can  we  say  that  it  is 
always  due  to  the  transfer  of  a  vegetable  from  the  contaminating 
to  the  contaminated  individual ;  that  in  all  these  cases  infection 
is  the  result  of  the  introduction  into  the  economy  and  of  the 
multiplication  of  a  vegetable  parasite?  No,  absolutely  ;  yes,  if 
we  are  content  to  enunciate  an  extremely  probable  hypothe- 
sis. We  surely  except  nervous  contagion,  which  results  from 
example. 

In  regard  to  diseases  of  a  contaminating  nature,  every  time 
that  we  have  found  an  explanation  of  contagion  it  has  been  that 
which  I  have  just  given  you  ;  no  other  has  been  verified,  no 
other  is  verifiable. 

Let  us  admit,  then,  at  least  provisionally,  that  each  contagious 
disease  is  produced  by  a  microbe.  Let  us  wait  until  positive 
proof  shall  be  furnished  for  those  in  which  the  microbe  has  not 
yet  been  demonstrated.  We  will  accept  without  astonishment 
the  announcement  of  its  discovery,  and  without  uneasiness  the 
delays  which  might  be  caused  by  that  demonstration.  Let  men 
trained  to  the  difficulties  and  to  the  refinements  of  microbio- 
logical research  give  us  this  fulfillment  of  demonstration,  and  it 
will  be  with  thanks  that  we  will  praise  every  one  of  their  discov- 
eries. The  role  of  the  physician  is  not  exclusively  to  seek  the 
infectious  agent;  but  it  ought  to  count  with  him.  To  speak  of 
microbe  in  the  place  of  virus  or  of  contagion  is  not  to  replace 
one  word  by  another ;  it  is  to  substitute  positive  knowledge  for 
ignorance  or  whim.  It  is,  at  the  same  time,  to  state  this  emi- 
nently practical  question  :  What  are  the  conditions  which  render 


INFECTION   IS   PRECEDED   BY   DISORDERED   NUTRITION.  5 

possible  the  development  of  the  microbe  ?  What  are  the  con- 
ditions which  ma}'  hinder  its  multiplication? 

What  renders  possible  the  development  of  an  infective  dis- 
ease is  not  the  chance  meeting  of  man  and  microbe.  This  meet- 
ing is  constant,  but  it  is  generally  without  result.  Microbes, 
even  the  most  dangerous,  assail  us.  They  are  spread  around 
us  with  the  same  prodigality  that  nature  distributes  develop- 
ing matter,  and  yet  growth  is  uncommon.  Infectious  disease, 
too,  is  only  an  accident,  because  the  infectious  agent  finds  only 
exceptional  circumstances  favorable, — I  do  not  say  to  its  pene- 
tration, but  to  its  development  and  its  multiplication. 

The  healthy  man  is  not  attractive  to  the  microbe.  Almost 
constantly  invaded  by  infectious  agents,  he  reacts  against  them, 
and  in  this  contest  keeps  generally  uppermost  to  such  a  point 
that  often  the  disease  does  not  even  become  apparent. 

It  is  not  thus  with  him  when  his  vitality  is  weakened ;  then 
his  means  of  defence  diminish.  Just  as  we  see  rushes  become 
covered  with  soil  where  certain  unusual  circumstances  are  op- 
posed to  the  natural  flow  of  water,  so  certain  microbes  may  in- 
vade the  human  organism,  whose  health  breaks  down,  whenever, 
by  the  fact  of  disordered  nutrition,  the  chemical  constitution  is 
modified. 

It  is,  therefore,  a  modification  antecedent  to  nutrition  which 
renders  infection  possible.  Disease  is  thus  the  result  of  two  dif- 
ferent processes,  one  of  which  can  only  act  by  means  of  the 
other.  In  short,  pathogenic  processes  are  rareljr  isolated  ;  in  the 
great  majority  of  cases  they  are  associated  and  combined. 

In  regard  to  this  complexity,  you  do  not  find  it  only  where 
there  is  question  of  contagion,  but  also  where  there  is  question 
of  the  most  simple  form  of  disease, — traumatism,  for  example. 
In  those  primary  and  elementary  forms  of  failure  of  nutrition 
where  the  cause  directly  attacks  certain  cellular  groups,  where  the 
cells  become  detached  from  each  other, — crushed,  soddened, — 
disease  will  scarcely  ever  be  established  by  this  unique  disor- 
der of  a  cellular  group.  Nearly  always  tranmatisn  will  dcirr- 
mine  the  putting  into  operation  of  new  pathogenic  processes, 
infection,  and  nerve  reactions.  Disorganization  of  cells  allows 
the  entrance  of  infectious  agents,  and  prepares  in  them  the  mat- 


6  LECTURES  ON    AUTO-INTOXICATION. 

ter  that  they  should  destroy.  Besides,  the  cause  which  is  capable 
of  inducing  alterations  falls  oftenest  upon  the  nerve  elements,  and 
through  them,  as  an  intermediary,  provokes  reflex  disturbances. 
Some  manifest  themselves  in. the  wounded  part,  where  the  irrita- 
tion of  blood,  absorption,  and  nutrition  cause  work  to  be  done 
in  an  abnormal  manner.  Others  reflect  upon  the  whole  economy  ; 
the  heart  contracts  oftener,  respiration  is  accelerated,  and  the 
elaboration  of  material  is  found  altered  in  all  the  cells  of  the  body. 
Urea  and  carbonic  acid  are  produced  in  much  greater  quantity. 
Nerve  reaction  has  not  only  added  certain  peculiar  features  to 
local  manifestations,  it  has  bound  the  whole  organism  to  the 
work  which  is  going  on  in  the  wounded  part. 

Besides,  nerve  reactions  nearly  always  borrow  the  co-opera- 
tion of  another  pathogenic  process.  Every  nerve  excitation, 
cold,  shock,  emotional  or  traumatic,  may  produce  syncope,  epis- 
taxis,  diarrhoea,  and  polyuria.  These  are  not,  then,  diseases. 
The  real  disease,  when  it  is  roused  by  nerve  reaction,  infers, — 
except  in  cases  where  the  intensity  of  the  stimulation  is  excessive 
and  those  wherein  the  nervous  system  is  abnormally  excitable, — 
infers — do  I  say  it  ? — an  essential  deterioration  of  the  organism. 

In  whom  does  a  draught  of  cold  determine  a  coryza  or  a 
bronchitis  ?  In  every  one,  will  you  say  ?  Perhaps  ;  but  especially 
in  those  whose  health  is  habitually  or  actually  altered.  Amongst 
the  diathetic,  especially  arthritic  or  scrofulous,  you  will  see 
this  fleeting  nerve  reaction  produce  in  them  lasting  effects ;  the 
coryza  is  tenacious  and  the  bronchitis  is  stubborn.  Disease 
will  quickly  follow  upon  nerve  reaction,  but  it  is  the  unavoid- 
able deterioration  of  the  organism  which  may  hasten  its  explo- 
sion, and  which  often  renders  it  persistent  and  chronic.  In  the 
non-diathetic  man,  for  the  present  weakened  or  indisposed,  dis- 
ease resulting  from  nerve  stimulation  will  be  not  less  prepared 
by  disturbance  of  nutrition,  although  the  disturbance  is  only 
transitoiy, — "  it  is  the  morbid  opportunit}',"  the  brief  diathesis 
of  the  authors  of  last  century.  Men  fatigued  by  overwork  or 
pleasure — exposed  to  depressing  influences — are  struck  by  con- 
ditions, real  and  disease-developing,  from  insignificant  nerve 
excitations,  which  would  have  produced  nothing  in  perfectly 
healthy  men. 


INFECTION   POSSIBLE   BY   INFLUENCES  UPON    NERVOUS   SYSTEM.        7 

Very  often  disease  induced  by  nerve  reflex — even  disease 
from  cold — is  an  infectious  illness,  and  we  have  not  onty  in  this 
particular  case  a  new  example  of  the  .association  of  the  two  dif- 
ferent pathogenic  processes,  but  we  find  here  the  association  of  a 
third  factor.  In  reality,  nerve  reaction  could  not  have  created 
infection  :  it  could  act  onlj'by  rendering  this  infection  possible; 
by  weakening  the  defence  which  the  healthy  organism  naturally 
opposes  to  microbes  ;  by  modifying  nutrition  so  as  to  develop  a 
chemical  medium  favorable  to  the  cultivation  of  vegetable 
organisms.  The  reaction  of  a  disturbed  nervous  system  induces 
temporary  disturbance  of  nutrition.  This,  in  its  turn,  opens 
the  way  to  infection  always  at  hand,  to  germs  always  present, 
which,  without  doubt,  have  to  fulfil  in  nature  another  part,  but 
which,  destined  to  destroy  dead  matter,  are  also  capable  of 
destroying  living  matter  when  they  find  it  in  a  state  of  prepara- 
tion. In  this,  perhaps,  lies  the  pathogenic  history  of  angina,  of 
pneumonia,  and  of  rheumatism. 

If  nerve  reaction,  by  corrupting  for  the  moment  nutrition, 
can  produce  the  morbid  opportunit3r,  it  may  also  modify  nutrition 
in  a  lasting  manner,  and  develop  diathesis,  but  it  will  be  the 
acquired  diathesis.  The  acquired  diathesis,  once  established, 
may  become  hereditarily  transmissible ;  and  if  you  go  back  to 
its  etiology,  be  it  in  the  individual  or  in  his  ancestors,  you  will 
easily  recognize  that  it  has  hud  for  its  origin  the  putting  into 
abnormal  play  of  nerve  reactions.  Let  a  bad  alimentary  hygiene 
— cold  and  moisture,  privation  of  air  and  light — cause  an  infant 
to  be  scrofulous,  and  let  the  permanence  of  the  same  causes 
keep  up  in  him  this  nutritive  disorder,  which  we  designate  under 
the  name  of  scrofulous  diathesis ;  or  let  a  young  man,  by 
Ii3'gienic  errors,  by  the  abuse  of  the  table,  by  protracted  studies 
at  night,  by  venereal  excesses,  l>y  nervous  shocks,  which  may 
be  the  consequence  of  complete  derangement  of  mind,  as  also 
of  a  jaded  brain,  develop  this  other  nutritive  disorder,  which  we 
designate  under  the  name  of  arthritism, — in  both  of  these  each 
cell  will  have  a  tainted  nutrition,  and  will  produce  cells  that 
maintain  the  same  nutritive  t}rpe.  And  amongst  these  cells  the 
generative  elements — ovule  or  spermatozoon — in  their  turn  will 
give  birth  to  the  cells  of  a  new  being,  whose  nutritive  activity 


8  LECTURES   ON   AUTO-INTOXICATION. 

will  be  similar  to  the  individual  that  has  begotten  them.  The 
acquired  diathesis  has  become  hereditaiy ;  it  does  not  recognize 
for  its  cause  in  the  descendants  the  vice  of  their  own  nerve 
reactions.  In  these,  nevertheless,  the  diathetic  state  really 
arises  from  nerve  perturbations  experienced  by  their  ancestors. 
There  are  certain  historical  families  whose  pathological  gene- 
alogy we  even  know,  and  where  the  reality  of  the  origin  of 
these  morbid  states  can  be  verified. 

The  diathetic  nutritive  disorder  is  more  than  a  morbid 
threatening  ;  it  is  disease  in  activity.  But  how  is  this  disease 
going  to  break  out  ?  It  is  generally  after,  the  operation  of  an 
external  cause  which  has  induced  nerve  changes ;  another 
example  of  the  necessary  association  of  several  pathogenic 
processes.  Here  is  an  arthritic ;  how  will  he  be  seized  with  an 
attack  of  gout?  Very  often  after  a  chill,  a  shock, — emotional 
or  from  injuiy.  Disease  thus  called  forth  in  the  course  of  a 
diathesis  is  an  episode,  a  paroxysmal  accident ;  but  this  acci- 
dent, this  episode,  may  appear  spontaneously,  as  the  consequence 
of  the  excess  of  the  nutritive  disorder  which  oftenest  recognizes 
as  its  determining  cause  nerve  change.  Some  people  persist  in 
not  making  this  distinction,  in  not  seeing  in  gout  anything  but 
the  gouty  accession;  so  much  so  that  gout  would  not  be  a 
disease,  but  a  succession  of  independent  diseases.  But  what 
explains  and  links  the  attacks  together  is  precisely  this  diathetic 
state,  which  I  consider  the  result  of  a  failure  of  nutrition.  The 
attack  of  gout,  on  the  contrary,  which  is  the  paroxysmal  acci- 
dent in  the  course  of  a  diathesis,  is  characterized  by  an  accelera- 
tion of  nutrition,  as  I  said  a  long  time  ago,  and  is  repeated 
to-day,  as  if  it  were  a  novelty  :  it  is  the  curative  attempt  which 
re-establishes  the  broken  equilibrium. 

If  nerve  shock  is  capable  of  thus  inducing  an  attack  of 
gout  in  an  arthritic  it  will  never  cause  it  in  an  individual  whose 
nutrition  is  not  weakened.  The  nutritive  derangement  which 
renders  possible  the  pathogenic  influence  of  nerve  reactions  fa- 
vors also  parasiticism.  Is  it  not  amongst  arthritics  that  you  see 
developed  by  preference  pityriasis  versicolor?  Is  it  not  amongst 
the  scrofulous  that  you  see  erysipelas  repeated  witli  a  truly  dis- 
heartening frequency  ?  I  have  multiplied  examples  sufficiently 


SEARCH    AFTER    MICROBES.  9 

to  be  able  to  say  that,  without  any  preliminary  change  in  nutrition, 
man  is  sheltered  from  infection.  I  have  excepted  syphilis, 
against  which  he  seems  unprotected.  It  is  because  several 
pathogenic  conditions  are  necessary  before  disease  can  be  pro- 
duced that  we  generally  resist  harmful  influences.  The  causes 
of  disease  are  innumerable ;  but,  in  order  to  attack  and  conquer 
us,  the}7  must  be  associated  ;  without  this  necessity  they  would, 
without  doubt,  have  annihilated  the  human  species. 

Thus,  only  to  deal  with  infectious  diseases,  I  am  right,  you 
see,  in  telling  you  now  that  the  physician  ought  not  to  allow 
himself  to  be  absorbed  alone  in  the  research  after  a  microbe.  He 
ought  to  occupy  himself  with  the  infectious  agent ;  but  he  ought 
also  to  retain  a  good  deal  of  his  anxiety  for  the  study  and  research 
of  circumstances  which  disarm  the  organism  against  the  invasion 
of  that  agent.  When  the  physician  shall  be  in  possession  of 
this  double  knowledge  that  man}' diseases  are  produced  by  mi- 
crobes, and  that  these  can  only  act  by  means  of  a  deterioration 
of  the  health,  resulting  from  various  pathogenic  processes,  he 
will  recognize  that  the  new  discoveries  contain  nothing  sub- 
versive, and  that  the  lessons  taught  by  ancient  medical  observa- 
tions are  not  compromised;  he  will  know  that  the  part  he  has  to 
play  is  still  the  same  to-day  as  it  was  twenty  years  ago,  and  that 
whilst  seeking  the  means  of  combating  microbes  he  ought  and 
he  will  always  be  obliged  to  sustain  the  forces  of  the  organism 
and  make  good  its  defence,  inspiring  himself  constantly  with  this 
truth  :  before  every  illness  there  is  a  disturbance  in  life, — for  nu- 
trition is  life.  What  can  bring  about  this  disturbance, — the  first 
step  to  be  overcome  before  becoming  ill  ?  It  may  bring  about  a 
change  in  the  production  or  distribution  of  the  forces  which  lib- 
erate certain  substances  elaborated  by  the  living  organism.  It 
may  modify  the  matter  itself, — augment  or  diminish  it, — whilst 
preserving  the  normal  proportion,  or  it  may  bring  about  dispro- 
portion of  the  constituent  elements  ;  it  may,  in  short,  cause  the 
appearance  of  abnormal  substances  through  perversion  of  the 
changes  associated  with  nutrition.  From  absolute  increase  of 
normal  matter,  or  the  production  of  abnormal,  intoxication  may 
be  developed. 

Substances  the  most  essential  to  the  constitution  of  the  body 


10  LECTURES   ON    AUTO-INTOXICATION. 

may  become  hurtful  when  they  accumulate.  If  the  subtraction 
of  water  is  dangerous,  its  excess  is  none  the  less  so  ;  it  changes 
the  conditions  of  osmosis ;  it  causes  a  swelling  up  of  the  cells, 
and  washes  out  their  dialysable  material ;  it  thus  disturbs  their 
chemical  constitution,  and  weakens  or  perverts  their  functional 
activity.  Mineral  substances  can,  by  their  excess,  equally  deter- 
mine accidents  that  are  truly  toxic, — the  salts  of  potassium  par- 
ticularly. The  most  important  excrementitious  material — car- 
bonic acid — could  not  be  retained  in  the  organism  a  few  minutes 
without  death  being  the  consequence.  The  biliary  acids  also,  if 
they  do  not  find  a  free  escape  outwardly,  produce  fatal  poisoning. 
All  the  soluble  ferments  elaborated  by  certain  glands  can  exer- 
cise a  poisonous  influence,  either  local  or  general.  We  find 
even  in  certain  secretions — in  saliva,  for  example — products  ex- 
tremely toxic,  and  which  are  not  ferments.  This  toxicity  is 
only  partly  due  to  alkaloids.  Whatever  opinion  we  may  have 
in  regard  to  the  origin  of  alkaloids,  it  is  certain  that  we  meet 
with  them  in  normal  tissues,  and  it  is  possible  that  they  may  be 
one  of  the  results  of  this  disassimilation  of  animal  cells ;  but  it 
is  not  demonstrated  that  these  alkaloids  of  the  normal  tissues 
are  toxic.  It  is  not  thus,  however,  with  the  alkaloids  of  certain 
products  of  secretion, — of  urine  in  particular.  Without  multi- 
plying examples,  you  see  that  the  augmentation  of  normal  sub- 
stances, either  by  increased  formation  or  retention,  can  induce 
quite  a  series  of  toxic  accidents,  some  of  which  have  already 
been  named,  such  as  asphyxia,  uraemia,  uricsemia,  cholsemia, 
glycaemia. 

Perverted  nutrition  leads  up  to  the  development  of  new  sub- 
stances which  may  become  toxic.  There  are  often  formed  in  the 
organism  peptones,  which  do  not  originate  in  the  intestinal  tube, 
but  which  are  injurious  in  this  sense,  that,  being  dialysable,  they 
escape  by  the  urine,  and  thus  bring  about  an  abnormal  spolia- 
tion of  the  organism.  There  are  thus  produced  abnormal  albu- 
mens, which  escape  by  the  kidneys,  and  seem  capable  of  destroy- 
ing the  nutrition  of  the  renal  epithelium  and  of  inducing  certain 
nephrites.  Disease  also  causes  the  appearance  of  abnormal 
coloring  matter  or  of  substances  transformable  into  coloring 
matter,  amongst  which  are  found  those  that,  in  urines,  take  on 


ACTION   OF    MICROBES  UPON    THE   TISSUES.  11 

a  red  coloration  under  the  influence  of  perchloride  of  iron.  I 
will  mention  leucin,  tyrosin,  and  all  the  imperfect  excre- 
mentitious  products  which  arise  from  insufficient  elaboration 
on  the  part  of  the  liver,  and  many  other  toxic  substances,  of 
which  I  know  neither  the  names  nor  the  constitution,  but 
whose  presence  in  morbid  urines  I  shall  demonstrate  to  yon 
physiologically.  All  these  substances  are  capable  of  producing 
forms  of  intoxication,  amongst  which  I  will  mention  eclampsia, 
acholia,  diabetic  coma,  and  many  other  grave  conditions,  as  also 
numerous  indispositions. 

If  intoxication  is  one  of  the  accidents  likely  to  arise  from 
disturbances  of  nutrition  let  us  see  what  infection  can  do.  We 
have  thought  over  many  of  the  hypotheses  bearing  upon  the 
mode  of  action  of  microbes.  But  if  the  anatomy  of  these  hurt- 
ful agents  is  scarcely  known  their  ph}-siology  is  still  less  known. 
We  have  imagined  that  they  act  in  five  different  ways.  We 
have  ascribed  to  them  a  mechanical  role,  supposing  that  they 
might  cause  obstruction  in  the  vessels,  more  particular!}-  those  of 
the  lung  and  the  kidney.  The  fact  is  perfectly  demonstrated  for 
charbon  and  for  the  septicaemia  of  Charrin  ;  but  the  microbes 
which  live  in  the  blood  are  rare — almost  the  exception.  It  is 
also  admitted  that  they  ma3T  induce  traumatic  changes, — erode 
and  perforate  cells.  This  is  a  hypothesis  whose  aid  I  called  in 
when  I  established  the  group  of  infectious  nephrites.  We  really 
find  microbes  in  the  organism, — in  urine, — and  we  find  a  lesion 
of  the  renal  epithelium.  It  is  admissible  that  they  have  broken 
through  this  epithelial  barrier,  and  that  in  their  course  through 
it  they  have  brought  about  its  deterioration  ;  but  in  this  there 
is  only  probability.  The  history  of  the  cholera  of  fowls  proves 
to  us  that  they  attack  muscular  fibre ;  in  certain  catarrhs  of  the 
bladder  and  vagina  they  penetrate  in  large  numbers  the  epithe- 
lial cells.  I  have  demonstrated  in  blennorrhagia  that  the  micro- 
coccus  of  Neisser  inhabits  essentially  the  protoplasm  of  the 
pavement  cells  of  the  urethra  or  of  the  conjunctiva,  and  that 
the  leucocytes  are  for  it  an  accessory  or  secondary  resting-place. 

It  is  also  said  that  microbes  cause  death  by  the  anatomical 
lesions  which  they  develop.  Assuredly  there  is  amongst  them 
those  which  produce  oedema,  haemorrhage,  suppuration,  emphy- 


12  LECTURES   ON   AUTO-INTOXICATION. 

sema,  and  gangrene ;  but  to  say  that  they  act  because  they  pro- 
duce these  effects  is  to  solve  the  problem  by  admitting  as  dem- 
onstrated that  which  is  still  a  matter  of  discussion  ;  the  essen- 
tial thing  would  be  to  know  by  what  process  they  determine 
such  local  lesions. 

This  fourth  hypothesis  has  been  enunciated  :  that  the  mi- 
crobe, in  order  to  nourish  itself,  consumes  what  is  useful,  the 
subtraction  of  which  is  prejudicial  to  the  organism.  The  ex- 
ample of  charbon  has  been  quoted  in  support  of  this,  and  its 
aerobic  bacteridium  takes  hold  of  the  oxygen  to  the  detriment 
of  the  blood-corpuscles.  This  ingenious  hypothesis  has  not 
even  received  the  beginning  of  demonstration. 

Lastty,  infectious  agents  can  produce  something  injurious, — 
can  elaborate  substances  that  are  toxic.  There,  at  least,  and 
there  only,  do  we  find  a  beginning  of  the  proof.  Indeed,  we 
know  a  good  many  bodies  produced  by  the  life  of  microbes.  We 
have  studied  in  the  fermentations  which  they  induce  in  the  flask, 
— carbonic  acid,  marsh-gas,  hydrogen,  even  sulphuric  acid,  am- 
monia, the  ammonia  compounds,  the  volatile  fatty  acids,  many 
complex  alkaloids  whose  toxicity  has  been  experimentally 
demonstrated,  indol,  phenol,  skatol,  etc., — all  can  poison,  for 
these  bodies  are  toxic.  They  besides  form  soluble  ferments, 
which  undoubtedly  play  a  part  in  the  production  of  local 
lesions  by  breaking  up  in  some  way  or  other  living  cells.  It  is 
therefore  certain  that  intoxication  in  part  arises  from  the  harm- 
ful action  of  microbes  ;  in  all  probability  such  is  the  part  they 
chiefly  play. 

It  is  not  only  in  infectious  diseases  that  we  have  to  reckon 
with  the  intoxication  produced  by  them,  it  is  also  in  the  normal 
state.  Indeed,  man,  -in  the  condition  of  physiological  life,  is 
inhabited,  for  a  considerable  length  of  his  digestive  tube,  by 
inferior  vegetables.  I  have  formerly  shown  you  the  toxicity  of 
intestinal  matter;  it  is  in  part  due  to  the  poisonous  products 
elaborated  by  these  microbes.  A  portion  of  these  products  is 
absorbed,  disease  may  prevent  their  elimination,  and  there  arises 
from  this  a  poisoning.  Intestinal  fermentation  increasing  ab- 
normally, the  heap  of  toxic  matter  may  become  such  that  its 
absorption  produces  intoxication  in  spite  of  the  integrity  of  the 


VARIOUS   MEANS  BY   WHICH   TOXIC   PRODUCTS   ARE   FORMED.        13 

renal  emunctory ;  it  is  to  this  cause  that  many  d}'speptic  acci- 
dents ought  to  be  referred.  Thus,  in  the  normal  as  in  the  patho- 
logical state,  the  organism  is  a  receptacle  and  a  laboratory  of 
poisons. 

The  object  of  the  lectures  which  follow  will  be  to  find  out 
what  part  is  played  by  self- intoxication  in  the  production  of 
disease  and  morbid  accidents. 


LECTURE  II. 
PRODUCTION  AND  ELIMINATION  OP  POISONS  BY  THE  ORGANISM. 

The  healthy  organism  receives  and  forms  poisons.     Constant  danger  of  auto- 
intoxication.    Means  by  which  the  organism  manages  to  escape  from  it. 

Origins  of  poisons  in  the  healthy  organism;  alimentation,  especially  min- 
eral substances ;  the  secretions  (saliva,  bile)  ;  digestion  and  intestinal 
putrefactions  ;  disassimilation  of  the  tissues.  The  blood  is  the  ebbing  and 

flowing  current  of  all  the  poisons. Demonstration  of  the  presence  of 

poisons  in  the  blood.  Direct  demonstration  is  still  incomplete.  Indirect 
demonstration  :  we  find  in  the  urine,  naturally  or  modified,  the  same  poisons 
as  in  the  digestive  canal  and  in  the  tissues ;  they  must,  therefore,  have  trav- 
ersed the  blood. Opinions  offered  to  explain  the  harmlessness  of  the 

poisons  of  the  digestive  canal.  Destruction  or  modification  by  dialysis  in 
passing  through  the  intestinal  mucous  membrane,  the  epithelium,  and  the 
capillaries  (Stich).  Hypothesis  relating  to  the  white  cells.  Protective  part 
played  by  the  liver,  which  stops  on  their  passage  alkaloidal  poisons  coming 

from  the  intestine  (Heeger),  and  destroys  them.    Experiments  of  Schiflf. 

Role  of  the  emunctory  organs  in  the  expulsion  of  poisons.  Intestinal 
emunction  :  the  putrid  diarrhoea  of  anatomists  ;  salutary  diarrhoeas.  Illu- 
sions relative  to  diarrhosa  spoken  of  as  supplementary  to  the  renal  emunction. 
Cutaneous  emunction :  elimination  of  water ;  perspiration  favorable  to 
elimination  of  poisons.  Elimination  of  volatile  fatty  acids :  odors  arising 
from  the  skin  when  nutrition  is  deranged.  Causes  of  the  death  of  animals 

which  have  been  varnished. Pulmonary  emunction,  carbonic  acid,  water, 

volatile  fatty  acids  :  fetidity  of  the  breath  in  those  who  are  constipated  and 

in  hypochondriacs. Renal  emunction  :  its  preponderating  influence.    The 

kidney  can  eliminate  all  toxic  products  except  gas.  Toxicity  of  urine  : 
danger  of  oliguria :  critical  polyuria  at  the  decline  of  fevers. 

I  HAVE  said  that  the  organism,  in  its  normal,  as  in  its  patho- 
logical state,  is  a  receptacle  and  a  laboratory  of  poisons. 
Amongst  these  some  are  .formed  by  the  organism  itself,  others 
by  microbes, — low  forms  of  vegetables, — which  either  are  the 
guests — the  normal  inhabitants — of  the  intestinal  tube,  or  are 
parasites  at  second  hand,  and  disease  producing.  Man  is  in  this 
way  constantly  living  under  the  chance  of  being  poisoned  ;  he 
is  alwaj^s  working  toward  his  own  destruction ;  he  makes  con- 
tinual attempts  at  suicide  by  intoxication.  And  yet  this  intoxi- 
cation is  not  realized,  for  the  organism  possesses  numerous 
resources  which  enable  him  to  escape  the  intoxication  which  is 
(14) 


PRODUCTION    AMD   ELIMINATION    OF   POISONS   BY   THE  ORGANISM.       15 

always  threatening.  He  throws  off  these  toxic  substances  into  a 
special  reservoir,  from  which  they  afterward  pass  outward;  and, 
besides,  the  blood  constantly  subtracts  from  the  organs  the 
poisons  as  soon  as  the}'  are  formed  in  them. 

I  have  shown  in  the  first  lecture  how  numerous  are  the  toxic 
substances  contained  in  the  organism.  In  the  first  rank  are 
placed  the  mineral  substances  introduced  with  our  food  ;  then 
come  the  products  of  physiological  secretion, — saliva  and  bile; 
the  products  of  digestion  ;  digestion,  too,  whilst  it  transforms 
albuminoid  substances  into  peptones,  also  gives  birth  to  alka- 
loidal  poisons;  and, lastly, toxic  substances  resulting  from  intes- 
tinal putrefactions.  Without  doubt,  the  stools  eliminate  the 
greatest  part  of  these  poisons  which  are  expelled  with  them, 
but,  nevertheless,  owing  to  the  slow  movement  of  the  intestinal 
contents,  the  mucous  membrane  absorbs  a  certain  part  of  them. 
We  find  in  the  close  relationship  of  our  tissues  other  poisons 
which  are  the  result  of  the  life  of  cells.  The}-  pass  out  into 
the  extra-cellular  fluids,  along  with  which  they  pass  into  the 
lymphatics  and  blood-vessels.  It  is,  therefore,  into  the  blood 
that  all  the  poisons  are  carried, — the  whole  of  those  that  are 
made  by  the  tissues,  and  part  of  those  which  are  formed  in  the 
digestive  tube.  Theoretically  we  cannot  conceive  how  things 
could  be  otherwise.  But,  evident  even  as  this  view  of  the  sub- 
ject appears,  it  must  be  demonstrated.  Direct  demonstration 
of  it  has  only  been  realized  in  a  very  incomplete  manner.  After 
ligature  of  the  colon,  Planer  found  H2S  in  the  blood  of  the 
portal  vein.  Carter  has  there  met  with  indigo  in  animals  the 
subjects  of  intestinal  derangements.  I  have  seen,  like  Gautier, 
alkaloids  not  only  in  the  tissues,  but  in  the  blood.  Here  is  a 
beginning  of  direct  objective  demonstration,  but  it  is  only  yet  a 
resemblance.  It  is  not  a  certainty. 


On  the  4th  of  December,  1884,  we  extracted,  by  means  of 
chloroform,  alkaloids  from  50  cubic  centimetres  of  muscle  of  beef. 
These  alkaloids,  soluble  in  chloroform,  give  precise  reactions  with 
the  following  reagents :  Tanret's  solution,  iodized  iodine,  phos- 
l>ko-inolybdate  of  soda  and  tannin.  September  3, 1884, a  healthy 
rabbit  is  killed,  then  cut  up  into  pieces;  it  weighs  thus  minced, 


16  LECTURES   ON    AUTO-INTOXICATION. 

without  the  abdominal  viscera,  1012  grammes.  It  is  digested  in 
2  litres  of  absolute  alcohol,  to  which  has  been  added  water  acidu- 
lated with  H2SO4,  and  this  macerates  for  two  days.  We  collect 
the  alcohol  as  it  is  filtered,  and  again  unite  it  to  the  alcohol 
which  bathed  the  muscles  of  the  animal,  and  which  we  obtain  by 
pressure.  We  have  thus  1896  cubic  centimetres.  We  evaporate 
at  40° ;  then  the  alcohol,  reduced  by  one-third,  is  evaporated  at 
80°  (we  lose  by  accident  one-third  of  this).  In  the  watery 
residue  we  find  all  the  reactions  usual  to  alkaloids.  The  precipi- 
tates obtained  are  abundant  with  the  following  reagents  :  Tanret, 
iodized  iodine,  phospho-molybdate  of  soda,  ferric  cyanide,  double 
iodide  of  potassium,  and  cadmium.  This  residue,  made  alkaline 
by  soda,  is  mixed  well  with  ether.  We  decant  the  ether,  which, 
shaken  up  well  with  a  little  HC1  that  has  been  added  to  it,  is  dis- 
tilled. The  residue  is  an  ethereal  extract.  It  is  precipitated 
fairly  well,  by  means  of  the  iodized  iodine  and  molybdo-phos- 
phate  of  soda  reagent. 


Indirect  demonstration  will  be  given  if  we  find  in  the  prod- 
ucts of  excretion  those  poisons  which  we  have  observed  in 
the  tissues  and  in  the  intestinal  canal;  and,  if  it  is  proved  that 
these  poisons  are  eliminated  by  organs  in  which  they  are  not 
formed,  the  logical  conclusion  will  be  that  the  blood  is  the 
necessary  medium  between  the  seat  of  the  formation  of  these 
poisons  and  their  place  of  elimination.  But  the  poisons  which 
exist  in  the  tissues  and  in  the  intestinal  canal  are  also  found 
in  the  urine,  either  naturally  or  modified  by  oxidation  or  united 
to  nitrogenous  or  sulphur  radicals  :  oxalic  acid,  in  the  state  of 
oxaluric  acid  ;  phenic  acid,  in  the  state  of  compound  sulpho- 
phenic  acid,  or  phenyl-sulphurous ;  bodies  of  the  aromatic 
series, — indol,  scatol,  cresol ;  butyric  acid,  as  in  the  stomach; 
lactic  acid,  as  in  the  stomach  and  first  part  of  the  intestine ; 
acetic  acid,  as  it  is  formed  under  certain  pathological  influences, 
in  considerable  quantity  in  the  whole  length  of  the  intestinal 
canal. 

We  also  find  alkaloids  in  the  urine  :  some  show  themselves 
in  a  modified  form,  as  quinine  ;  others  naturally,  and  without 
having  undergone  any  previous  alteration.  Amongst  these  alka- 
loids some  are  soluble  in  chloroform,  others  are  insoluble  in  this 
body,  but  soluble  in  ether ;  both  are  found  in  the  urine,  with  the 


REASON   WHY   TOXIC   ACCIDENTS   ARE   INFREQUENT.  17 

same  characters  as  in  the  intestine.  There  is  nothing  in  physiol- 
ogy which  warrants  us  in  considering  all  these  bodies  as  products 
elaborated  by  the  kidney ;  it  is  the  blood,  therefore,  which 
carries  them  there.  One  of  the  first  authors  occupied  in  the 
experimental  investigation  of  these  intoxications  (Stichj  thought 
that  the  poisons  of  the  intestinal  canal  must  be  neutralized, 
destroyed,  or  undergo  modifications  which  would  deprive  them 
of  their  toxicity,  consequent  upon  their  passage  through  the 
absorbent  membranes  of  the  intestinal  canal,  which  played  the 
part  of  a  dyalyser,  through  the  epithelial  cells  and  through  the 
walls  of  the  capillaries.  He  is  astonished  to  find  so  many 
poisons  in  the  intestinal  canal  and  yet  so  few  toxic  accidents ; 
and,  considering  that  the  poisons  of  the  intestinal  canal  are 
innocuous  to  the  animal  which  has  formed  them,  whilst  the  same 
poisons  become  harmful  to  an  animal  of  any  other  species  into 
which  they  have  been  introduced  by  the  rectum  or  stomach,  he 
is  led  to  think  that  each  kind  of  animal  has  the  power  of  destroy- 
ing of  itself  the  poisonous  substances  which  it  forms.  This  is 
a  view  of  the  matter  of  which  we  have  no  demonstration. 

According  to  Hoffmeister,  the  white  globules  play  a  part 
in  the  transformation  of  peptones  into  albumen,  since  we  no 
longer  find  in  the  emunctories  the  peptones  which  we  have 
injected  into  the  blood.  We  could,  perhaps,  apply  this  hypoth- 
esis of  Hoffmeister  to  the  destruction  of  poisons,  and  say 
that  the  toxic  substances  corning  from  the  intestinal  canal  are 
neutralized  in  the  blood  by  the  white  globules.  To  explain 
the  harmlessness  of  the  poisons  of  the  intestinal  canal,  we  have  in 
addition  invoked  the  protective  action  of  the  liver.  This  organ 
stops,  arrests,  as  we  know,  certain  portions  of  our  food ;  it 
impedes  the  passage  of  grape-sugar  and  stores  up  glucose 
under  the  form  of  glycogen.  It  plays  also  a  protective  part 
in  arresting  alkaloidal  substances.  Heeger  has  injected  into  the 
portal  vein  blood  containing  alkaloids  (nicotine,  strychnine,  mor- 
phine, quinine).  The  blood  examined  coming  from  the  liver 
contains  less  of  these ;  the  substances  injected  have  diminished 
by  one-fourth  or  one-half.  Perhaps  the  liver  places  itself  in 
opposition  to  all  the  poisons  of  the  organism,  and  robs  it  of 
the  blood  which  carries  them. 

2 


18  LECTURES   ON    AUTO-INTOXICATION. 

Schiff  has  revived  the  question.  He  operates  with  nicotine. 
The  same  dose  of  this  substance  which,  introduced  into  a 
peripheral  vein,  kills  an  animal,  does  not  kill  another  animal  of 
the  same  weight  if  we  inject  it  into  a  branch  of  the  portal 
vein.  Schiff  introduces  a  quantity  of  nicotine  into  the  intestinal 
canal  of  an  uninjured  animal,  and  it  is  not  found  to  be  intoxi- 
cated by  it.  The  same  dose  intoxicates  the  animal  if  we  have 
ligatured  its  portal  vein,  for  then  the  toxic  substance  reaches 
the  general  circulation  by  the  accessories  of  the  portal  venous 
system,  without  having  passed  through  the  liver,  which  would 
have  arrested  it. 

Fresh  liver  is  triturated  with  nicotine.  An  infusion  of  this 
is  injected  into  an  animal,  and  it  does  not  kill  it.  The  same 
dose  of  nicotine  ground  up  with  an  equal  weight  of  renal  or 
muscular  tissue  kills  it.  The  liver  is  not  alone  content  in 
arresting  these  poisons ;  it  destroys  them.  These  facts  have 
been  experimentally  verified  in  my  laboratory  by  C.  H.  Roger, 
who,  as  regards  this  question  of  the  protection  of  the  organs 
by  the  liver,  has  added  to  our  knowledge  many  new  facts, 
which  I  shall  have  occasion  to  describe  to  you.  But  the  alka- 
loids are  not  the  most  poisonous  substances  of  the  organism. 
This  explanation  is  right  as  regards  them,  but  is  not  applicable 
to  all ;  it  is  necessary  to  add  to  it  this  other  piece  of  information, 
— that  man  escapes  intoxication  by  the  intestinal,  cutaneous,  pul- 
monary, and  renal  emunctions. 

The  part  played  b}'  the  intestinal  emunctory  in  the  elimina- 
tion of  certain  poisonous  substances  is  attested  by  the  com- 
monly fetid  stools  of  persons  who  frequent  the  post-mortem 
theatre.  Their  fetid  character  recalls  the  putrid  odor  of  the 
emanations  from  the  cadavera.  Sometimes  this  emunction  is 
defective  ;  for,  if  the  largest  part  of  the  toxic  material  is  thus 
expelled,  a  part  is  absorbed  ;  there  is  a  defective  circle  for  cer- 
tain molecules  of  poisons.  We  find  in  the  intestine  toxic  sub- 
stances arising  from  the  disassimilation  of  matter, — taurocholic 
and  glycocholic  acids,  or  their  derivatives,  cholic  and  cholalic 
acids,  dyslysin,  a  b'ody  formed  by  the  liver,  afterward  trans- 
formed in  the  intestine.  We  find  these  mineral  salts  formed 
out  of  bile  or  secreted  by  the  intestinal  glands  themselves.  The 


IMPROBABILITY   OF    VICARIOUS   FUNCTION.  19 

intestine  also  contains  gases  which  are  not  all  formed  there ; 
there  are  individuals  in  whom,  in  a  very  short  time,  an  excessive 
tympanitis  is  developed.  In  such  cases  certain  gases  are 
probably  secreted  by  the  digestive  canal.  I  do  not  know  what 
they  are,  nor  even  whether  they  are  analogous  to  those  which 
bring  about  fermentation.  We  find  hydrocarbons,  sure  enough  ; 
nitrogen  probabty  ;  perhaps  carbonic  acid,  and  even  ox}-gen, 
since  certain  aerobic  microbes  live  in  the  intestine.  To  what 
extent  are  these  gases  poisonous?  It  is  difficult  to  reply  to  this 
question.  Those  which  produce  hysterical  tympanitis  do  not 
appear  to  be  poisonous. 

From  these  facts  follow  certain  applications  that  may  be 
made  to  pathology.  Has  it  not  been  said  now  for  a  long  time 
past  that  there  are  "  salutary  diarrhoeas  ? "  People  who  have 
lived  for  several  years,  the  subjects  of  diarrhoea,  and  retain- 
ing the  appearance  of  perfect  health,  have  seen  their  diarrhoea 
and  their  health  disappear  at  one  and  the  same  time.  We  may  de- 
rive from  these  facts  some  encouragement  in  inducing  diarrhoea 
in  certain  cases,  without,  however,  raising  exaggerated  hopes 
in  any  one,  the  subject  of  a  supplementary  diarrhoea,  of  his  being 
able  to  compensate  the  insufficienc}'  by  another  emunctory.  We 
have  spoken  of  the  intestine  acting  vicariously  for  the  kidney 
by  discharges  of  serum.  For  my  part,  I  scarcely  believe  in 
vicarious  functions  any  more  for  the  skin  than  for  the  intestine. 
In  increasing  more  actively  the  cutaneous  and  intestinal  secre- 
tions we  remove  a  considerable  quantity  of  water  from  the 
organism,  but  not  what  ought  to  be  eliminated  dissolved  in  the 
water.  There  is  a  certain  quantity  of  material  associated  with 
a  determined  quantity  of  water,  according  to  the  emunctory  by 
which  the  water  is  thrown  out.  If,  for  example,  there  is  in  the 
blood  0.15  gramme  of  urea  for  1000  grammes  of  water,  the  urine 
carries  away  15  grammes  of  urea  for  every  1000.  The  sweat 
will  only  carry  awa}r  0.15  gramme  for  every  1090,  exactly  the 
proportion  which  is  found  not  in  the  blood,  but  in  the  liquor 
sauguinis.  Then  1  kilogramme  of  water,  which  by  the  renal 
channel  would  have  carried  away  15  grammes  of  urea,  only 
carries  away  30  centigrammes  by  the  skin  and  the  intestine. 
One  emunctory  can  scarcely  vicariate  for  another. 


20  LECTURES   ON    AUTO-INTOXICATION. 

By  the  skin  are  eliminated  water,  salts  in  small  quantity, 
carbonic  acid,  and  some  volatile  fatty  acids.  Copious  perspira- 
tions may  be  useful  in  certain  intoxications, — caused  by  poisons, 
for  instance, — not  because  they  eliminate  the  poisons  themselves, 
but  probably  because  they  expel  from  the  organism  the  abnormal 
products  which  it  has  formed  under  the  influence  of  the  poisons. 

In  many  putrid  intoxications  amongst  individuals  who  are 
the  subjects  of  deep-seated  foul  sores  the  odor  of  the  skin  recalls 
that  of  their  suppuration.  What  enables  us  to  understand 
the  useful  part  played  by  the  perspiration  in  the  cure  of  these 
morbid  states  is  the  odor  which  the  skin  takes  under  the  influence 
of  certain  disorders  of  nutrition.  Amongst  hypochondriacs — 
the  alienated,  living  in  absolute  inactivit}r,  and  with  defective 
alimentation — fatty  acids  are  eliminated  more  abundantly  by  the 
skin.  From  this  arises  the  odor  special  to  the  places  inhabited 
by  men  forced  to  this  kind  of  life, — the  odors  of  asylums,  of 
prisons,  barracks, — odors  which  differ  one  from  the  other. 
When  nutrition  is  deranged,  by  depressing  influences  acting 
through  the  intermediary  of  the  nervous  system,  we  may  be 
warned  of  its  being  so  by  the  odor. 

There  is  in  existence  an  experimental  demonstration  of  the 
part  which  the  cutaneous  emunctory  plays  in  the  elimination  of 
toxic  substances.  We  know  that  the  varnishing  of  the  skin  of 
animals  produces  a  marked  fall  in  the  heat  of  the  body.  Is  this 
the  result  of  failure  of  the  cutaneous  respiration  ?  It  is  hardly 
probable.  Is  it  due  to  the  action  of  the  vaniish  upon  the  nerve 
terminations  ?  Why,  this  reflex  action  is  much  less  than  faradi- 
zation, the  application  of  cold  or  of  heat ;  besides,  what  these 
forms  of  irritation  of  the  tissues  determine  is  albuminuria,  not 
haematuria,  convulsions,  and  reduced  temperature.  What  is 
special  to  the  varnishing  is  perhaps  the  retention  of  poisonous 
substances  which  the  skin  ought  to  eliminate. 

By  the  lungs  are  eliminated  carbonic  acid  (1100  grammes  in 
twenty-four  hours),  water,  ammonia  sometimes,  and  often  volatile 
fatty  acids,  which  explain  the  fetid  character  of  the  breath  of 
people  the  subjects  of  constipation  and  of  hypochondriasis,  and 
which  are  the  result  of  a  depraved  nutrition  or  of  an  incomplete 
destruction  of  matter.  By  the  lungs,  too,  are  eliminated  poi- 


KIDNEYS,  THE    MOST   IMPORTANT   ELIMINATING   ORGANS.  21 

sonous  substances  scarcely  known,  to  •which  Du  Bois-Reymond 
has  drawn  attention,  especially  the  volatile  poisons  accidentally 
introduced  into  the  digestive  canal  (alcohols,  ethers,  chloroform, 
asa  foetid  a). 

But  of  all  the  organs  of  elimination  the  most  important  is 
the  kidnejr.  One  cannot,  as  in  the  case  of  the  intestine,  reproach 
•it  with  being  a  defective  emunctory,  capable  of  re-absorbing  a 
part  of  the  products  which  it  eliminates.  Absorption  does  not 
take  place  in  the  urinary  channels,  at  least  in  the  normal  con- 
dition. If  there  is  produced  a  desquamation  of  epithelium, 
intoxication,  it  is  true,  shows  itself;  it  is  then  a  complex  thing, 
resulting  not  only  from  the  re-absorption  of  substances  which 
the  kidney  ought  normally  to  eliminate,  but  from  poisonous  sub- 
stances which  the  decomposing  urine  forms  in  the  urinary  chan- 
nels under  the  influence  of  ferments  which  are  found  there. 

What,  then,  does  the  kidney  eliminate?  Everything  save 
gaseous  material:  in  the  first  place,  water;  then  two-thirds,  at 
least,  of  the  solid  matter,  especially  mineral  matter,  of  which  you 
will  not  be  slow  in  recognizing  the  eminently  poisonous  power; 
many  nitrogenous  substances  (urea,  coloring  and  odoriferous 
material).  Certainly,  all  these  substances  are  not  poisonous, 
but  many  of  them  are.  What  is  certain  is  that  urine,  taken 
altogether,  is  toxic.  We  have  always  regarded  oliguria  as  a 
troublesome  thing ;  whereas,  on  the  contrary,  at  the  declination 
of  fevers,  a  critical  polyuria  is  nearly  always  useful,  because  it 
expels  poisonous  substances  formed  by  the  economj*  during  the 
illness.  There  may  arise  unpleasant  symptoms,  according  to  the 
relative  impermeability  of  the  kidney  for  certain  substances. 


LECTURE  III. 

PRELIMINARIES  TO  THE  EXPERIMENTAL  STUDY  OP  THE  TOXICITY 
OF  THE  PRODUCTS  OF  EMUNCTION. 

Necessity  of  demonstrating  experimentally  that  the  retention  of  excrementitious 
material  may  cause  intoxication.  Pulmonary,  intestinal,  and  cutaneous 
emunctories  are  inconvenient  for  this  demonstration.  Choice  of  the  urinary 

secretion  for  research  upon  the  toxicity  of  the  products  of  emunction. 

Comparison  of  the  various  methods  employed  by  the.  experimenter  for 
introducing  in  to  the  organism  substances  the  toxicity  of  which  he  wishes  to 
study.  Introduction  by  the  digestive  canal  and  subcutaneous  injection 
inconvenient.  Advantages  of  iutra-venous  injection.  Its-  harmlessness ; 

its  facility.     Uniformity  of  the  results  obtained. Study  of  the  action 

consequent  upon  the  liquids  employed  to  serve  as  excipieuts  in  the  injection 
of  poisonous  substances, — water,  alcohol,  glycerin. 

THERE  exists,  as  we  have  said,  in  the  organism  an  incessant 
tendency  to  toxaemia  from  accumulation,  and  from  which  it  es- 
capes by  various  means,  thanks  to  the  part  plaj'ed  by  the  liver, 
which  forms  an  active  barrier  to  poisons  taken  from  the  digestive 
tube,  but  is  insufficient  -for  those  formed  in  the  tissues, — thanks 
especially  to  the  safeguard  which  is  established  through  the 
einuuctory  apparatus.  In  order  that  intoxication  may  be 
avoided,  it  is  necessar3T  that  the  five  emunctory  offices  should  be 
in  a  state  of  anatomical  and  functional  integrity;  that  the  blood, 
the  circulatory  apparatus,  and  the  nervous  system  should  func- 
tionate normally.  Everything  caught  in  the  meshes  of  these 
organs  may  cause  intoxication.  It  seems,  at  least,  that  this 
should  be  so  ;  but  appearance  may  not  be  real :  presumption  is 
not  demonstration. 

If  I  say  that  death  nearly  always  arises  from  intoxication, — 
because,  in  nearly  all  diseases,  it  is  asphyxia  which  puts  a  ter- 
mination to  all  vital  acts,  and  that  asphyxia  is  an  intoxica- 
tion,— I  seem  to  be  formulating  a  syllogism  which  is  indisput- 
able. Yet  it  is  only  a  sophism,  however,  for  asphyxia  is  a 
(22) 


STUDY   OP   THE   TOX1CITY   OF   THE   PRODUCTS   OF   EMUNCTION.       2<J 

complicated  thing,  and  if  intoxication  from  excess  of  carbonic 
acid  is  one  of  its  factors  want  of  oxygen  is  another.  There 
is,  then,  no  idea  so  reasonable  as  that  which  requires  demon- 
stration. Consequently,  we  ought  to  prove  that  the  retention 
of  substances  destined  to  be  eliminated  by  the  emunctories  is 
capable  of  producing  intoxications  in  the  doses  in  which  these 
substances  are  formed  in  the  normal  organism.  The  problem 
to  be  solved  is  to  seek  for  the  measure  of  the  activity  of 
the  toxic  substances  which  are  eliminated  in  twenty-four  hours 
by  all  the  emunctories  combined, — and  what  enables  us  to  de- 
termine this  in  a  given  time  is  the  quantity  of  poison  capable 
of  intoxicating  a  known  weight  of  living  matter.  We  cannot 
set  ourselves  to  solve  this  problem  with  any  emunctory  that  we 
choose. 

Thus,  amongst  emunctories  whose  failure  to  functionate 
can  contribute  to  intoxication  of  the  organism  the  lung  is 
be3'ond  all  dispute:  without  counting  the  other  toxic  substances 
it  eliminates,  the  carbonic  acid  which  it  exhales  in  twenty-four 
hours  would  poison  a  man  a  great  number  of  times. 

The  intestine  does  not  offer  a  soil  for  useful  experiments,  for 
we  are  powerless  to  make  the  distinction  between  toxic  products 
which  are  brought  there  by  the  secretions  and  those  which  are 
formed  therein.  In  regard  to  the  skin,  researches  are  embarrass- 
ing, on  account  of  the  small  quantity  of  products  secreted  and 
of  the  difficulty  which  we  have  of  collecting  them.  It  is,  there- 
fore, from  the  urinary  tract  that  we  will  seek  for  the  demonstra- 
tion of  the  toxicity  of  the  products  of  emunction  ;  by  it,  is 
reserved  the  speciality  of  eliminating  toxic  substances  which  are 
not  volatile,  a  deduction  being  allowed  for  that  which  is 
destroyed  in  the  liver  and  in  the  totality  of  the  organism. 

What  methods  are  allowed  to  us  for  the  introduction  into  the 
organism  of  toxic  substances  ?  Ingestion  by  the  digestive  canal 
is  an  illusory  method.  We  are  obliged  to  dilute  the  toxic  ma- 
terials to  make  them  acceptable.  We  introduce  them  into  an 
organ  which  is  continually  eliminating  by  the  stools  a  part  of 
its  contents.  How  can  we  know  what  quantit}'  of  that  which 
we  have  introduced  has  been  absorbed?  Besides,  absorption 
from  the  intestinal  canal  is  very  slow,  and  the  organism  has 


24  LECTURES   ON   AUTO-INTOXICATION. 

time  to  protect  itself  by  eliminating  the  poison.  M.  Morel- 
Lavalle'e  has  communicated  to  the  Clinical  Society  the  following 
fact :  In  a  patient  who  had  ingested  60  grammes  of  laudanum 
from  2  o'clock  in  the  morning  to  8  o'clock  in  the  morning, 
washing  out  of  the  stomach  removed  45  grammes  of  the  poison. 
In  six  hours  one-fourth  only  of  the  poison  had  been  absorbed. 
When  we  proceed  to  the  introduction  of  toxic  substances  by 
means  of  the  digestive  canal  we  never  can  know  if  what  has 
been  introduced  has  been  absorbed,  and  we  run  the  risk  of 
being  forced  to  consider  substances  inoffensive  whi«h  are  really 
poisonous. 

Injection  by  the  subcutaneous  cellular  tissue  is  liable,  in 
great  part,  to  be  similarly  criticised;  elimination,  it  is  true,  will 
only  be  made  by  the  blood,  but  absorption  is  slow,  whilst 
emunction  is  rapid.  It  is,  therefore,  difficult  to  form  an  exact 
appreciation  of  the  quantity  of  the  injected  substance  which  is 
contained  in  the  blood  at  the  precise  moment  at  which  such  a 
phenomenon  shows  itself.  Besides,  the  injection  produces  by 
itself  certain  disturbances  which  may  cloak  the  action  proper 
to  the  injected  substance.  It  is  painful,  and  provokes  nervous 
reactions.  It  causes  particularly  albumin uria  ;  the  injection  of 
4  cubic  centimetres  of  water  by  the  subcutaneous  method  in  the 
case  of  a  rabbit  induced  this  phenomenon. 

There  remains  the  intra-venous  channel.  The  dangers  which 
were  attributed  to  it  at  first  are  erroneous.  It  is  almost  as  easy 
and  quick  from  the  operative  point  of  view  as  injection  into  the 
cellular  tissue;  'it  is,  besides,  more  searching,  more  inoffensive, 
and  less  painful.  Thanks  to  it,  we  can,  in  a  period  equal  to  a  com- 
plete revolution  of  the  blood,  distribute  through  the  whole  of 
the  organism  a  known  quantity  of  poisonous  material,  and  know 
exactly  what  dose  is  contained  in  the  blood  at  the  moment  in 
which  there  bursts  forth  the  first  indication  of  toxicity. 

I  have  made  comparisons  between  injections  of  saccharified 
urine  into  the  intra-venous  channels  and  subcutaneously.  When 
this  is  introduced  directly  into  the  blood  glycosuria  shows  itself 
three  minutes  after  the  beginning  of  the  injection. 


STUDY   OF   THE    TOXICITY   OF   THE   PRODUCTS   OP    EMUNCTION.      25 


INTRA-VENOUS   INJECTION    OF   DIABETIC   URINE. 

On  the  llth  of  December,  1884,  into  a  rabbit  weighing  1645 
grammes,  we  injected  into  the  veins  133  cubic  centimetres  of 
urine  containing  traces  of  albumen  and  60  grammes  of  sugar  to 
the  litre.  The  urine  is  filtered  and  neutralized.  The  quantity 
of  urine  injected  represents  4.85  grammes  of  sugar  for  each  kilo- 
gramme of  the  animal  and  63.05  grammes  for  each  kilogramme 
of  blood.  At  the  33d  cubic  centimetre,  emission  of  urine  already 
rich  in  sugar.  Toward  the  71st  cubic  centimetre,  fresh  emission 
of  urine,  richer  in  sugar  than  the  first,  and  sufficiently  albumin- 
ous. At  the  end  of  the  injection,  third  emission  of  urine,  still 
richer  in  sugar  than  the  two  preceding.  The  temperature,  one 
hour  after,  stood  at  36.4°  C.  (97.5°  F.).  An  hour  and  a  half 
after  the  injection  the  urine  is  found  still  to  contain  sugar. 

December  12th.  The  urine  contains  a  less  quantity  of  sugar. 
Temperature,  40°  C.  (104°  F.). 

December  13th.     Trace  of  sugar;  no  albumen. 

December  23d.     The  animal  is  quite  well. 


The  same  quantity  introduced  by  the  cellular  tissue  does  not 
produce  glycosuria,  because  absorption  is  so  slow  that  the  blood 
destroys  the  sugar  as  it  is  absorbed,  without  giving  it  time  to 
reach  the  kidney. 

SUBCUTANEOUS   INJECTION   OF   DIABETIC  URINE. 

Sixty -five  cubic  centimetres  of  the  same  urine  are  injected 
into  the  cellular  tissue  of  a  rabbit  weighing  1750  grammes, — 
about,  therefore,  2.2  grammes  of  sugar  for  each  kilogramme  of 
the  animal.  After  the  injection  the  urine  of  the  rabbit  does  not 
contain  sugar ;  it  is  albuminous. 

December  12th.  No  sugar.  Temperature,  40.1°  C.  (104.2° 
F.).  In  the  evening  the  animal  dies.  At  the  autopsy,  in  the 
region  in  which  the  injection  was  made,  one  sees  neither  suppu- 
ration nor  gangrene,  but  a  reddish  liquid,  full  of  mobile  organ- 
isms, round,  very  small,  which  one  also  finds  in  the  liver,  and 
which  appear  also  to  exist  in  the  blood. 


The  intra-venous  method  is  the  less  harmful,  much  as  this  may 
appear  paradoxical.  One  hundred  grammes  of  fluid  injected  into 
the  blood  are  not  followed  by  any  accident.  The  same  quantity 


26  LECTURES   ON    AUTO-INTOXICATION. 

of  this  fluid,  purified,  or  even  previously  raised  to  a  temperature 
of  100  degrees,  if  we  inject  it  under  the  skin,  causes  the  animal  to 
die  from  septic  accidents.  It  is  possible  that  some  of  the  in- 
fective agents  derived  from  the  intestinal  tube  or  from  without 
cause  the  appearance  of  something  in  the  cellular  tissue,  modified 
by  the  presence  of  the  injected  fluid,  which  is  capable  of  killing 
the  animal;  whereas,  on  the  contrary,  when  we  inject  into  the 
veins  fluid  even  in  appearance  septic,  a  liquid  rendered  opales- 
cent by  the  presence  of  bacteria,  there  may  result  from  this  no 
accident,  or  albuminuria  at  the  most. 


INTRA-VENOUS  INJECTION  OF    URINE   RENDERED  OPALESCENT   BY 
THE   PRESENCE   OF   BACTERIA. 

November  8,  1884.  Urine  of  a  patient  the  subject  of  arterio- 
sclerosis. Quantity  passed  in  twenty-four  hours,  850  grammes. 
This  urine  is  albuminous ;  it  contains  moving  microbes,  in  the 
form  of  rods,  short  and  numerous  enough.  Neutralized,  and 
slightly  alkalinized  and  filtered,  it  is  injected  into  the  veins  of 
a  rabbit  weighing  1580  grammes.  The  quantity  injected  is  135 
cubic  centimetres  in  eleven  minutes, — about  86  for  each  kilo- 
gramme of  the  animal.  The  temperature  of  the  rabbit  before 
the  injection  was  40°  C.  (104°  F.).  It  lulls  to  37.2°  C.  (99°  F.) 
immediately  after.  Myosis  shows  itself  slowly  :  it  only  appears 
toward  the  80th  cubic  centimetre.  There  is  emission  of  very 
little  urine.  After  the  injection  the  animal  remains  lying  on  its 
side  ;  its  respiration  is  slow.  The  reflexes  are  hardly  percep- 
tible. At  the  end  of  twenty  minutes  the  temperature  is  37.8°  C. 
(100°  F.)  ;  the  animal  is  upon  its  paws. 

It  has  lost  0.8  X  2.8  X  1580  calorics  =  3539  calorics. 

The  urine  has  absorbed  12.2  X  0.135  calorics  =  1647  calorics. 

The  rabbit,  therefore,  has  made  less  by  1892  calorics. 

November  10th.     The  animal  has  traces  of  albumen. 
November  15th.     It  is  quite  well. 


Perhaps  bacteria  are,  after  a  time,  neutralized  by  the  oxygen 
of  the  blood,  especially  if  they  are  anaerobic  bacteria,  or  if  they 
are  the  common  bacteria  which  have  not  yet  exercised  their 
influence  except  upon  dead  matter.  We  can  inject  thousands  of 


INTRA-VENOUS   INJECTION   OP   TOXIC    MATERIAL.  21 

millions  of  certain  bacteria  without  the  organism  being  the 
least  disturbed  by  it.* 

The  process  of  intra-venous  injection  is  applicable  to  every- 
thing that  is  soluble  except  oxygen.  Nevertheless,  it  has  been 
proposed  at  the  Academy  of  Sciences  to  make  intra-venous  in- 
jections of  oxygenized  water.  The  splitting  up  of  this,  as  I 
have  observed,  would  be  immediate,  and  would  end  in  gaseous 
pulmonary  embolism.  At  most,  I  have  only  seen  experimental 
injections  utilized  as  a  method  of  study,  and  not  their  appli- 
cation to  therapeutics.  Intra-venous  injections  of  medicines 
into  the  bodies  of  men  ought,  according  to  the  new  order,  only 
to  be  employed  in  cases  altogether  exceptional, — in  cholera,  for 
example, — or,  as  I  have  already  once  said,  in  a  disease  certain 
to  be  speedily  fatal, — confirmed  hydrophobia. 

It  remains  for  us,  before  proceeding  with  the  injection  of 
toxic  substances,  to  study  how  liquids  behave  physiologically 
which  serve  for  the  dissolution  of  those  substances.  The 
only  excipients  employed  are  water,  alcohol,  and  glycerin.  In 
the  rabbit,  distilled  water,  at  a  temperature  very  notably  below 
that  of  the  blood,  only  commences  to  show  itself  toxic  when  we 
inject  more  than  90  cubic  centimetres  of  it  for  each  kilogramme 
of  the  animal, — say  for  100  grammes  of  blood  117  of  water. 
Death  ensues  with  122  cubic  centimetres  for  each  kilogramme  of 
the  animal ;  that  is,  157  grammes  of  water  to  100  of  blood. 
Absolute  alcohol  is  toxic  beyond  0.6  cubic  centimetre  for  eacli 

*  Watson  Cheyne,  in  his  "  Lectures  on  Suppuration,"  delivered  at  the  Royal  Col- 
lege of  Surgeons,  London,  February,  1888,  has  shown  how  the  disease  which  is  experi- 
mentally produced  stands  related  to  the  number  of  micro-organisms  injected.  Taking 
cultivations  of  proteus  vulgaris,  for  example,  he  found  that  -fa  cubic  centimetre  of 
an  undiluted  cultivation  was  rapidly  fatal  when  injected  into  a  rabbit,— the  quantity 
injected  contained  250,000,000  of  bacteria  ;  also,  that  56,000,000  bacteria  caused  exten- 
sive abscess,  the  animal  dying  in  from  six  to  eight  weeks.  Fewer  than  18,000,000 
seldom  produced  any  effect.  In  diseases  of  this  nature,  however,  many  things  have 
to  be  considered,— not  only  the  quantity  injected,  but  the  virulence  of  the  micro- 
organisms and  the  susceptibility  of  the  animal.  Mice  are  peculiarly  susceptible  to 
septicaemia;  the  injection  of  a  single  bacillus  has  induced  death,  whilst  4  cubic 
centimetres  of  a  jelly  cultivation,  and  which  contained  myriads  of  bacilli,  could  be 
injected  into  the  ear  of  a  rabbit  without  causing  more  than  slight  constitutional 
disturbance  and  local  redness  with  swelling,  which  lasted  only  a  few  days.  In  the 
case  of  staphylococcns  pyogenes  aureus,  Cheyne  showed  (Brit.  Med.  Journal,  March 
10,  1888)  that  it  was  necessary  to  inject  1.000,000,000  cocci  into  the  muscles  of  rabbits 
in  order  to  cause  a  rapidly  fatal  result ;  250,000,000  produced  simply  a  small  circum- 
scribed abscess.— T.  O. 


28  LECTURES  ON   AUTO-INTOXICATION. 

kilogramme  of  the  animal.  The  clot  which  it  produces  immedi- 
ately redissolves  in  the  blood  coming  from  other  veins,  and  there 
arises  no  embolon  from  it.  The  more  alcohol  is  diluted,  the  more 
we  can  inject  of  it.  The  degree  of  dilution  the  most  favorable 
is  20  grammes  for  each  100  \>y  volume, — 20  cubic  centimetres  of 
absolute  alcohol  for  80  cubic  centimetres  of  water ;  1.45  cubic 
centimetres  of  absolute  alcohol  carried  to  this  degree  of  dilution 
produce  narcosis  and  comaj  3  cubic  centimetres  kill.  For  each 
100  grammes  of  blood  it  is,  then,  necessary  to  take  2  cubic  centi- 
metres of  alcohol  to  produce  narcosis  and  3.9  cubic  centimetres 
to  bring  about  death. 

Glycerin  is  less  toxic  than  alcohol.  We  cannot  employ  pure 
glycerin ;  it  produces  viscid  emboli.  We  must  prefer  dilu- 
tion of  it  to  50  for  each  100.  We  establish  that  5  cubic  centi- 
metres of  anhydrous  glycerin  for  each  kilogramme  of  the 
animal  produce  muscular  tremors,  and  that  14  cubic  centimetres 
induce  death,  with  immediate  cadaveric  rigidity.  We  know, 
then,  for  the  future,  that  the  substance  whose  toxic  power  we 
wish  to  test  by  intra-venous  injection  ought  not  to  be  dissolved 
in  more  than  90  cubic  centimetres  of  water, — in  more  than  1.45 
cubic  centimetres  of  alcohol,  diluted  in  the  proportion  of  20  to 
each  100,  or  5  cubic  centimetres  of  glycerin,  diluted  in  the  pro- 
portion of  50  to  100  for  each  kilogramme  of  the  animal. 


LECTURE  IY. 

ON   THE    TOXICITY   OF    URINES. 

Admitted  from  all  time  by  physicians,  the  toxicity  of  uriue  has  only  recently 

been  demonstrated. Cl.  Bernard  and  Frerichs  have  stated  the  question. 

Isolated  study  of  some  of  the  toxic  elements  of  certain  urines:  Gabriel  Pou- 
chet.  Study  of  the  toxicity  of  urine  taken  in  its  entirety — negative  conclu- 
sion: Murou.  Positive  conclusion:  Feltz  and  Ritter,  Bocchi  aud  Schiifer. 

Study  of  certain  pathological  urines:  Lepine,  Dupard,  and  Gudriu. My 

owii  experiments  upon  the  toxicity  of  normal  urine  injected  en  masse  by 
intra-venous  channel.  Reply  to  certain  objections  raised  against  this  method. 

Choice  of  the  rabbit  as  the  animal  to  exhibit  reactions. Physiological 

phenomena  consequent  upon  the  intra-venous  injection  of  normal  urine, — 
myosis,  accelerated  respiration,  torpor,  polyuria,  fall  of  temperature  due  to 
diminished  heat  production  ;  survival  or  death,  according  to  the  dose  injected. 
Discussion  upon  the  possible  causes  of  death.  Determination  of  the  unity  of 
toxicity.  Urotoxy.  Urotoxic  co-efficient.  Toxicity  of  urines  different 
according  to  whether  they  have  been  secreted  during  the  waking  hours  or 
sleep. 

WE  have  said  that  if  the  organism  forms  poisons  and  yet  is 
not  poisoned,  it  is  because  the  liver  stops  some  of  them  and 
that  the  rest  are  eliminated.  The  safeguard  to  the  economy 
resides  in  having  an  organ  of  arrest  and  in  the  emunctories. 
We  have  admitted  this  idea  hypothetically,  but  we  have  recog- 
nized the  necessity  of  verifying  experimentally  this  view  of  the 
matter,  reasonable  as  it  appears  to  us.  From  amongst  possible 
demonstrations  we  have  chosen  that  which  consists  in  prov- 
ing that  the  emunctories  really  cast  out  externally  toxic  sub- 
stances and  that  the  excrementitious  products  are  toxic.  For 
various  reasons,  which  we  need  not  recall,  we  have  addressed 
ourselves,  in  order  to  verify  the  toxicity  of  excrementitious 
products,  to  those  which  the  kidney  eliminates,  and  we  have 
adopted  the  intra-venous  injection  as  the  experimental  method. 

Are  urines  toxic  ?  To  this  question  we  have  at  all  times  re- 
plied in  the  affirmative, — so  much  so  that  there  is  no  necessity 
to  raise  the  question  again.  Upon  this  undebated  point  has 
been  built  the  thepry  of  uraemia.  Urine  is  toxic  :  thus,  when  it 
ceases  to  be  secreted  the  organism  is  poisoned.  We  may  say 

(29) 


30  LECTURES   ON   AUTO-INTOXICATION. 

that  this  is  a  true  medical  opinion  of  the  matter ;  but,  true  as  it 
appears  to  be,  it  claims  demonstration.  Cl.  Bernard  raised  the 
question  ;  Frerichs  has  followed  it  up.  Physicians  and  physi- 
ologists have,  after  these,  emulously  striven  to  find  out  what  are 
the  substances  to  which  urine  owes  its  toxicity, — ammonia,  urea, 
etc.  In  all  these  researches  it  is  not  of  the  urine  itself  that  there 
is  question,  but  certain  substances  which  we  find  in  it  or  which 
are  developed  in  it  in  consequence  of  catalytic  changes, — car- 
bonate of  ammonia,  for  example.  It  is  the  study  of  certain  toxic 
substances  of  the  urine  which  we  have  at  length  broached,  and 
not  that  of  the  toxicity  of  urine  in  kind.  We  have  blamed  the 
coloring  matter,  odorous  and  volatile,  and  mineral  matters, — 
potass  in  particular.  They  are,  without  doubt,  toxic  ;  but  they 
constitute  only  a  part  of  the  toxicity  of  urines. 

M.  Gabriel  Pouchet  has  found  in  normal  urine  alkaloids 
chemically  similar  to  the  toxic  alkaloids.  In  1882  I  extracted 
from  certain  urines  taken  from  patients  the  subjects  of  infectious 
diseases  alkaloids,  with  which  I  have  been  able  to  produce,  ex- 
perimentally, dilatation  of  the  pupil,  acceleration  of  the  beats 
of  the  heart, — physiological  effects  which  approach  those  of 
atropine.  But  the  question  here  was  one  of  abnormal  alkaloids, 
or  at  least  of  alkaloids  extracted  from  the  urines  of  sick  people. 
It  is  by  repeated  attempts,  made  in  various  ways,  that  we 
approach  the  solution  of  the  problem. 

The  question,  taken  in  its  entirety,  dates  from  1868.  Muron, 
having  made  subcutaneous  injections  of  urine,  affirms  the  non- 
toxicity  of  it ;  but  the  method  which  he  adopted  ought  to  put 
us  into  a  state  of  mistrust ;  we  have  seen  why.  MM.  Feltz  and 
Ritter  (in  1881)  made  intra-venous  injections  of  urine  just 
as  it  is,  and  have  concluded  for  the  toxicitj7  of  urine.  Bocchi 
(at  the  end  of  1882)  repeated  the  experiments,  and  also  con- 
cluded that  urine  is  toxic,  considered  as  a  whole.  He  has  sub- 
cutaneously  injected  normal  urine  into  frogs,  and  has  killed  them  ; 
but  amongst  mammalia — the  rat  and  guinea-pig — he  has  not 
produced  the  toxic  phenomena  which  he  met  with  in  the  frog. 
In  April,  1883,  Schiffer  employed  ethereal  extracts  of  urine. 
He  killed  frogs  with  the  extract  taken  from  16  to  25  grammes  of 
urine,  and  rabbits  with  a  quantity  of  extract  which  represents 


URINE   NOT   TOXIC   FROM   ITS   ACIDITY   ONLY.  31 

1^  litres  of  urine;  but  if  he  has  demonstrated  the  toxicity  of 
a  product  contained  in  urine,  he  has  not  elucidated  the  problem 
of  the  toxicity  of  normal  urine  in  man,  for,  according  to  these 
experiments,  it  would  be  necessary,  while  the  due  proportions 
were  observed,  that  man  should  retain  in  his  body  a  quantity  of 
urine  equal  to  his  own  weight  in  order  to  be  intoxicated  by  it. 
The  experiment  of  Schiffer  only  proves  that  urine  contains 
something  which,  in  excessive  dose,  may  become  toxic.  Very 
interesting  experiments,  regarded  from  a  physiological  point  of 
view,  were  made  in  1883  and  1884  by  M.  Dupard,  under  the 
inspiration  of  M.  Lupine,  and  afterward  by  MM.  Lepine  and 
Guerin  ;  but  as  these  experimenters  only  made  use  of  pathologi- 
cal urines,  the  results  obtained  do  not  demonstrate  the  toxicit}- 
of  normal  urines.  It  is  necessary  to  return  to  the  method  sug- 
gested b}<  Feltz  and  Hitter, — the  injection  of  normal  urine  just 
as  it  is;  that  is  what  I  have  done,  as  these  authors  did  in  1883 
and  1884,  by  intra-venous  channels. 

It  seems  at  first  sight  unlikely  that  one  could  introduce  into 
the  vascular  system  urine  as  it  is  ;  and,  before  everj'thing  else,  it 
is  necessary  to  reply  to  certain  objections  which  cannot  fail  to 
be  raised  against  the  legitimacy  of  this  proceeding.  And,  first, 
can  we,  without  causing  accidents,  introduce  into  the  blood  a 
considerable  quantity  of  water,  such  as  that  which  would  serve 
as  a  vehicle  for  the  solid  matter  of  the  urine?  We  said  in 
the  preceding  lecture  that  we  can  inject  without  danger  into 
the  blood  up  to  90  cubic  centimetres  of  water  for  each  kilo- 
gramme of  the  animal.  Can  we  inject  urine  as  it  is  with  an  acid 
reaction?  Do  we  not  run  the  risk  of  attributing  to  the  action 
of  urine  effects  which  would  be  sufficiently  determined  by  the 
introduction  of  a  nornwlljr  acid  bod)'  into  an  alkaline  medium? 
Theoretically  we  cannot  afford  to  overlook  this  possible  cause 
of  error,  although  there  may  be  reason  for  us  asking  ourselves 
if  it  concerns  the  theory  of  intoxication  by  retention  in  the 
blood  of  urine  not  secreted,  and  if  the  acidity  might  not  be 
due  to  the  action  only  of  the  renal  secretion.  We  see  neutral 
salts  which  have  become  acid  after  having  undergone  dialysis ; 
it  is  there  a  borrowed  acid.  In  every  case  it  would  not  be  legiti- 
mate to  compare  the  effects  of  the  retention  of  neutral  urine 


32  LECTURES   ON   AUTO-INTOXICATION. 

with  the  injection  of  acid  urine.  In  fact,  I  have  acknowledged 
that  the  question  of  the  reaction  is  a  thing  of  indifference.  At 
first  the  urine  is  acid  to  a  feeble  degree ;  it  contains  few  free 
acids;  the  acidity  is  chiefly  due  to  acid  salts.  I  have  injected, 
for  the  sake  of  comparison,  and  without  obtaining  differences  in 
the  results,  acid  urines  and  the  same  urines  exactly  neutralized 
by  carbonate  of  soda.  Yet,  to  be  more  cautious,  I  have,  in  all 
my  experiments,  exactly  neutralized  the  urines  before  injecting 
them  into  the  blood.  It  is  a  precaution  which  cannot  diminish 
the  toxicity  of  urines,  and  which  puts  in  the  shade  the  objection 
announced  higher  up.  That  admitted,  we  cannot  inject  into  the 
blood  of  an  animal  normal  urine  without  determining  physio- 
logical phenomena  and  death  with  doses  generally  less  and  often 
much  inferior  to  those  in  which  distilled  water  is  toxic. 

The  phenomena  which  I  am  going  to  describe  have  been  ob- 
served exclusively  in  the  rabbit.  The  rabbit  is  the  best  animal 
to  choose  when  there  is  question  of  injecting  into  the  veins.  The 
posterior  marginal  vein  on  the  dorsal  part  of  the  face,  as  it 
spreads  over  the  ear,  easily  allows  of  penetration  taking  place, 
without  preliminaiy  removal  of  the  skin,  by  means  of  a  Pravaz 
syringe.  We  can,  even  in  the  rabbit,  penetrate  directly  into  the 
median  artery  of  the  ear.  The  choice  of  this  animal  singularly 
diminishes  the  difficulties,  and  especially  the  slowness,  of  intra- 
venous injections.  The  guinea-pig,  which  offers  the  same  ad- 
vantages, scarcely  lends  itself  so  well  for  experiments  in  the 
laboratorjr,  for  there  are  economical  necessities  before  which  it 
is  necessary  to  bow. 

The  first  phenomenon  which  follows  the  intra-venous  injec- 
tion of  normal  urine  is  contraction  of  the  pupil.  After  the 
injection  of  10,  12,  or  15  cubic  centimetres  of  urine  there 
appears  a  myosis,  which  goes  on  gradually  increasing  until  the 
pupillary  opening  becomes  pin-pointed.  A  little  after  the  begin- 
ning of  the  injection  we  notice  acceleration  of  respiratory  move- 
ments, with  a  diminution  of  their  range.  Then  the  animal  is 
enfeebled,  its  movements  become  irregular  and  laborious ;  somno- 
lence now  comes  on.  We  remark,  also,  increase  in  the  urinary 
secretion  and  frequency  of  voiding  the  urine.  Urine  increases 
more  than  any  other  material  the  urinary  secretion.  The  diu- 


EFFECTS  OF    THE   INTRA-VENOUS   INJECTION   OF   URINE.  33 

resis  induced  by  the  injection  of  distilled  water  is  not  to  be 
compared  to  that  produced  by  the  injection  of  normal  urine. 
At  the  same  time,  the  temperature  falls.  This  fall  is  constant, 
it  is  true,  after  every  intra-venous  injection  of  liquid,  but  it  is 
much  more  considerable  after  the  injection  of  urine.  The 
amount  of  heat  lost  by  the  animal  is  greater  than  that  neces- 
sary to  raise  to  the  temperature  of  the  blood  the  quantity  of 
liquid  injected.  It  is  a  thermic  fall,  which  is  dependent  upon  a 
diminution  of  heat  production.  The  temperature  of  the  rabbit 
falls  from  39°  C.  (102.2°  F.)  or  37°  C.  (98.6°  F.)  to  32°  C. 
(89.6°  F.);  the  hypothermia  of  itself  in  certain  cases  may  ex- 
plain the  death. 

We  also  notice  a  diminution  of  the  palpebral  and  corneal  re- 
flexes ;  often,  too,  exophthalmos.  Death  comes  at  last,  without 
convulsion  or  with  moderate  muscular  tremors,  with  persistence 
of  the  cardiac  beats,  and  of  contractility  of  the  striated  and  unstri- 
ated  muscular  fibre.  The  pupil  remains  contracted  after  death, 
then  it  dilates  again  in  some  of  the  cases.  If  the  smallest  dose 
of  urine  is  injected, — sufficient  to  produce  coma,  but  not  death, 
— the  animal  remains  passive,  with  respiratory  movements  of 
feeble  range;  chilled;  with  pupillary  contraction;  and  with  a 
polyuria  such  that  every  two  minutes  an  emission  of  urine  takes 
place.  The  superficial  vessels  are  dilated ;  the  arteries  beat  with 
such  amplitude  that  their  pulsations  are  easily  felt  up  to  the  tip 
of  the  ear.  Then  torpor  diminishes,  the  fall  of  temperature  is 
arrested,  heat  production  goes  on  again,  and  the  pupil  dilates. 
At  the  end  of  half  an  hour  return  to  health  is  definite,  without 
secondary  phenomena.  The  animal  may  be  kept  under  observa- 
tion for  weeks  or  months,  without  our  being  able  to  observe  in 
it  any  pathological  accident.  One  fact  to  note  is,  that  we 
rarely  set  up  albuminuria  unless,  for  the  most  part,  an  albumi- 
nuria  which  is  very  slight  and  very  fleeting  in  the  animals  which 
survive.  On  the  contrary,  after  the  injection  of  pathological 
urines — certain  kinds,  at  least — albuminuria  is  constant  and 
notable  ;  one  may  witness,  too,  luematuria. 

What  quantit}'  of  normal  urine  is  necessary  to  produce 
intoxication  by  intra-venous  injection?  This  is  a  difficult  ques- 
tion to  decide.  The  oscillation  habitually  takes  place  between 


34  LECTURES  ON   AUTO-INTOXICATION. 

30  and  60  cubic  centimetres  for  each  kilogramme  of  the  animal, 
— 45  cubic  centimetres,  on  an  average.  Pupillary  contraction 
often  begins  to  show  itself  after  the  employment  of  10  cubic 
centimetres.  The  urine  of  a  subject  in  whom  abundant  drinks 
had  produced  a  normal  polyuria  has  been  injected  with  im- 
punity up  to  97  cubic  centimetres  for  each  kilogramme  of  the 
animal, — a  dose  in  which  distilled  water  is  already  toxic.  The 
urine  of  this  same  individual,  who  was  submitted  to  a  chill 
without  becoming  febrile,  has  killed  with  a  dose  of  12  cubic 
centimetres  for  each  kilogramme  of  the  animal.  The  variations 
of  toxicity,  already  large  in  the  limits  of  the  normal  state, 
become  still  more  considerable  as  we  reach  the  border  of  the 
pathological. 

Pathological  urines  am  not  always  more  toxic  than  normal 
urines  ;  they  may  be  less ;  they  may  differ  from  them  in  pro- 
ducing other  symptoms.  Certain  pathological  urines  determine, 
with  a  dose  of  10  cubic  centimetres,  convulsions,  which  we 
hardly  ever  observe  after  the  injection  of  normal  urines.  With 
certain  others  it  is  necessary,  in  order  to  induce  a  phenomenon 
of  some  kind  or  other,  to  inject  as  much  urine,  and  even  more, 
than  the  dose  in  which  distilled  water  causes  death.  Thus,  dis- 
ease sometimes  augments,  sometimes  it  diminishes  the  toxicity 
of  urine.  Amongst  certain  albuminurias  the  innocuous  nature 
of  the  urine  is  a  remarkable  fact ;  the  kidney  seems  to  have 
separated  from  it  the  toxic  substances,  retaining  them  within 
the  organism. 

When  death  follows  an  injection  of  urine,  we  may  suppose 
that  it  results  from  the  mechanical  action  of  the  mass  of  urine 
injected  or  from  dilution  of  the  blood.  It  is  not  so ;  for  we 
can  double  and  almost  treble  the  mass  of  blood  without  inconve- 
nience. Nor  is  death  more  to  be  attributed  to  the  general  hydra- 
tion  of  the  bodjr.  If  we  reduce  by  evaporation  the  quantity  of 
urine  lay  one-half,  only  expelling  the  water  from  it,  the  toxicity 
is  doubly  increased.  The  degree  of  concentration  of  a  healthy 
urine  causes  its  toxicity  to  vary  :  a  healthy  man,  but  oliguric,  is 
more  toxic  than  the  polyuric,  so  far  as  regards  an  equal  quan- 
tity of  urine,  which  proves  that  the  urine  does  not  kill  by  the 
water,  but  by  the  substances  which  are  in  a  state  of  solution 


ON    THE   TOXICITY   OF   URINES.  35 

in  the  water.  Whatever  those  substances  may  be,  it  is  interest- 
ing to  know  the  degree  of  toxicity  that  they  communicate  to 
urines ;  that  is  to  say,  the  toxic  power  of  the  matter  which  is 
elaborated  by  a  given  weight  of  man  and  is  eliminated  in  a 
given  time  by  his  urine. 

It  has  appeared  to  me  necessary,  for  the  clearness  of  later 
explanations,  to  create  a  new  name,  and  I  excuse  n^-self  for 
doing  so.  This  neologism  has  for  its  object  the  denomination 
of  the  unit,  which  will  serve  as  a  term  of  comparison  in  the 
estimation  of  the  variations  of  the  toxicity  of  urine.  I  shall 
call  the  unit  of  toxicit}'  "urotoxy";  that  is  to  say,  the  toxic 
amount  necessary  to  kill  a  kilogramme  of  living  matter.  This 
unit  we  shall  determine  by  experiment.  I  shall  stucty  thus  the 
urotoxic  co-efficients;  that  is  to  say,  the  quantity  of  urotoxies 
which  1  kilogramme  of  man  can  form  in  twenty-four  hours. 

A  healthy  man,  weighing  60  kilogrammes,  passes  in  twent}'- 
four  hours  1200  cubic  centimetres  of  urine.  If  50  cubic  centi- 
metres of  this  urine  kill  1  kilogramme  of  animal,  1200  cubic 
centimetres  ought  to  kill  24  kilogrammes  of  the  animal ;  then  60 
kilogrammes  of  man  make  and  eliminate  l>y  the  kidneys  in  twenty- 
four  hours  what  would  kill  24  kilogrammes  of  animal.  Thus, 
1  kilogramme  of  man  forms  in  twenty-four  hours  what  would 
kill  400  grammes  of  an  animal.  In  order  to  kill  1  kilogramme 
it  is  necessary  to  have  1  urotoxy.  The  urotoxic  co-efficient  of 
this  man  of  60  kilogrammes  is  thus  0.4.  This  is  almost  the 
normal  co-efficient,  which  I  have  found  to  be,  on  an  average, 
0.464. 

If  1  kilogramme  of  man  forms  in  twenty-four  hours  what 
is  sufficient  to  kill  464  grammes  of  animal,  he  forms  in  twenty- 
four  hours  almost  one-half  of  what  is  necessary  to  kill  himself. 
On  an  average  of  two  days  and  four  hours  man  makes  a  mass  of 
urinary  poison  capable  of  intoxicating  himself.  There  are  varia- 
tions in  the  normal  state  for  the  urotoxic  co-efficient,  but  they 
are  limited.  In  the  pathological  state  the  urotoxic  co-effick-nt 
raivly  exceeds  2  and  rarely  descends  below  0.10. 

The  toxicity  of  normal  urines  varies  according  to  numerous 
circumstances, — cerebral  activity,  muscular  activity,  sleep,  diet- 
ing, etc.  The  variations  bear  upon  the  intensity  and  upon  the 


36  LECTURES   ON    AUTO-INTOXICATION. 

quality  of  this  toxicity.  The  urines  of  sleep,  although  more 
dense, — more  rich  in  solid  matter, — are,  in  equal  volumes,  almost 
always  less  toxic  than  the  urines  of  the  day.  In  an  equal  time 
the  urines  secreted  during  sleep  always  contain  an  amount  of 
material  less  toxie  than  that  secreted  during  the  day.  Man 
elaborates  during  sleep  from  two  to  four  times  less  poison  than 
during  an  equal  time  of  cerebral  activity. 


TOXICITY   OF   THE   URINES   FORMED   DURING   THE   DAY   AND   OP 
THOSE   FORMED   DURING   SLEEP. 

September  15,  1885.  We  gather  the  urine  of  twenty-four 
hours  of  a  healthy  adult  man  weighing  81  kilogrammes  and  700 
grammes.  These  urines  are  collected  in  three  portions  correspond- 
ing to  the  periods  of  secretion,  having  in  each  a  duration  of  eight 
hours.  The  first  portion  commences  from  the  moment  of  waking 
— quarter  past  7  in  the  morning — to  quarter  past  3  after  mid- 
day (morning  period);  the  second  portion  from  quarter  past '3 
to  quarter  past  11  at  night  (evening);  the  third  portion  from 
quarter  past  11  to  quarter  past  7  on  the  following  morning 
(sleep). 

Urine  of  Eight'  Hours — the  Morning  Period. — Quantity,  865 
cubic  centimetres ;  density,  1027.  This  acid  urine  is  exactly 
neutralized  by  bicarbonate  of  soda,  filtered,  and  injected  into 
a  vein  of  the  ear  of  a  rabbit  weighing  1750  grammes.  The 
rectal  temperature  of  the  rabbit  before  the  operation  was 
39.6°  C.  (103.2°  F.) ;  owing  to  its  not  moving  about,  the 
temperature  fell  at  the  beginning  of  the  injection  to  39.2°  C. 
(102.6°  F.).  Contraction  of  the  pupil  began  when  the  animal 
had  received  25  cubic  centimetres ;  at  33  cubic  centimetres, 
emission  of  urine ;  at  35  cubic  centimetres,  restlessness,  re- 
spiratory arrest,  loss  of  palpebral  and  corneal  reflexes ;  death. 
At  this  moment  the  temperature  was  at  39.3°  C.  (102.8°  F.). 
The  heart  still  continued  to  beat  for  some  little  time.  The 
temperature  of  the  urine  injected  was  26°  C.  (78.8°  F.).  The 
animal  was  killed  by  the  injection  of  85^>00  =  2(>  cubic  centi- 
metres of  urine  for  each  kilogramme  of  the  animal. 

Urine  of  the  Eight  Hours  Belonging  to  the  Evening  Period. — 
Quantity,  320  cubic  centimetres;  density,  1028;  reaction,  acid; 
neutralized  and  filtered ;  this  urine  is  injected  into  the  vein  of 
a  rabbit  weighing  1560  grammes.  At  the  beginning  of  the 
injection  the  rectal  temperature  of  this  rabbit  was  40°^C.  (104° 
F.).  At  3  cubic  centimetres,  quickened  respiration;  at  28 


TOXICITY   OF   URINES   PASSED   DURING   THE   DAY    AND   NIGHT.       37 

cubic  centimetres  myosis  commences,  and  is  complete  at  36  cubic 
centimetres  ;  at  35  cubic  centimetres,  excessive  movement ;  at  39 
cubic  centimetres,  convulsions,  opisthotonos,  death.  The  heart 
continues  to  beat.  The  rectal  temperature  at  the  moment  of 
death  is  39.8°  C.  (103.6°  F.).  The  temperature  of  the  urine 
injected  was  23°  C.  (73.4°  F.).  The  animal  was  killed  by  the 
injection  of  39^00  =  25  cubic  centimetres  of  urine  for  each  kilo- 
gramme of  animal. 

Urine  of  the  Eight  Hours  of  Sleep. — Q.uantity,  220  cubic  cen- 
timetres; density,  1031;  reaction,  acid.  This  urine,  neutral- 
ized and  filtered,  was  injected  into  a  vein  in  the  ear  of  a  rabbit 
weighing  1600  grammes.  At  the  beginning  of  the  injection  the 
rectal  temperature  was  40.2°  C.  (104.5°  F.).  After  6  cubic  cen- 
timetres had  been  injected  there  was  quickened  respiration. 
At  21  cubic  centimetres  myosis  had  begun  ;  at  33  cubic  centi- 
metres, clonic  convulsions;  at  34  cubic  centimetres,  loss  of 
palpebral  reflexes,  exophthalmos,  and  momentaiy  suspension  of 
respiration;  at  46  cubic  centimetres, very  severe  clonic  convul- 
sions ;  then  opisthotonos  and  death.  The  heart  continued  to  beat. 
The  rectal  temperature  at  the  moment  of  death  was  39.9°  C. 
(103.8°  F.).  The  temperature  of  the  urine  injected  was  23°  C. 
(73.4°  F.).  The  animal  was  therefore  killed  by  the  injection  of 
— ^ — =28.75  cubic  centimetres  of  urine  for  each  kilogramme 
of  animal. 

In  equal  volumes,  the  urines  of  the  morning  period,  although 
less  dense,  are  more  toxic  than  the  urines  of  the  evening  period. 
The  totality  of  the  urines  of  the  morning  period  is  represented 
by  \Y  =  18.25  urotoxies.  The  totality  of  the  urines  of  the 
evening  period  represents  352g°  =  12.8  urotoxies.  The  urines  of  the 
sixteen  hours  of  da}'  represent,  therefore,  31.05  urotoxies;  or, 
by  the  hour,  1.9406;  or,  by  the  hour  and  per  kilogramme  of  man 
who  has  furnished  the  urines,  0.02375.  During  one  hour  of  wake- 
fulness  this  man  has  therefore  eliminated  on  an  average  per  kilo- 
gramme of  his  weight  a  quantity  of  urinary  poison  capable  of 
destroying  23.75  grammes  of  living  tissue.  In  equal  volumes, 
the  urines  of  sleep,  although  more  dense,  are  less  toxic  than 
the  urines  of  wakefulness.  The  totality  %of  the  urines  of  eight 
hours  of  sleep  represents  7.65217  urotoxies;  or,  by  the  hour, 
0.956521  ;  or,  by  the  hour  and  per  kilogramme  of  the  man  who' 
bus  farnished  the  urines,  0.0117  urotoxies.  One  kilogramme  of 
man,  during  one  hour  of  sleep,  eliminates,  therefore,  a  quantity 
of  urinary  poison  capable  of  destroying  11.7  grammes  of  living 
tissue.  In  sixteen  hours  of  wakefulness  this  person  has  elimi- 
nated per  kilogramme  what  would  kill  380  grammes  of  animal, 
and  in  eight  hours  of  sleep  he  has  eliminated  what  would  kill  93.6 


38  LECTURES   ON   AUTO-INTOXICATION. 

grammes  of  animal.  In  the  twenty-four  hours  (waking  and 
sleeping)  he  has  thus  eliminated  a  quantity  of  urinary  poison 
capable  of  destroying  437.6  grammes  of  animal.  The  urotoxic 
co-efficient  of  this  man  was  therefore  0.4736.  From  this  we 
conclude  that,  to  kill  1  kilogramme  of  living  matter,  it  would 
have  required  for  each  kilogramme  of  this  man  two  days,  two 
hours,  and  forty-three  minutes. 

On  September  19,  1885,  we  gathered  the  urine  of  twenty-four 
hours  of  a  healthy  adult  man  weighing  81  kilogrammes,  700 
grammes.  This  urine  had  been  received  in  two  portions, — 
one  corresponding  to  the  sixteen  hours  of  wakefulness  and  the 
other  corresponding  to  the  eight  hours  of  sleep. 

Urine  of  Sixteen  Hours  of  Wakefulness. — Quantity,  700  cu- 
bic centimetres  ;  density,  1028 ;  urea,  24.4  grammes  for  every 
1000,  or  17.08  grammes  for  the  whole  of  the  wakeful  period  ; 
reaction,  slightly  acid.  This  urine,  neutralized  and  filtered,  is 
injected  into  a  vein  of  the  ear  of  a  rabbit  weighing  1720  grammes. 
The  rectal  temperature  at  the  beginning  of  the  injection  was 
40.3°  C.  (104.6°  F.).  At  the  time  that  23  cubic  centimetres 
of  urine  have  been  injected  myosis  commences ;  the  pupil  is 
pin-pointed  at  33  cubic  centimetres;  at  36  cubic  centimetres, 
exorbitism,  agitation  ;  at  43  cubic  centimetres,  respiratory  pause ; 
at  46  cubic  centimetres,  loss  of  e}relid  and  corneal  reflexes, 
death  without  convulsions.  The  heart  continued  to  beat.  The 
pupils  continued  pin-pointed  after  death.  The  rectal  temperature 
at  the  time  of  death  was  39.5°  C.  (103.2°  F.).  The  temperature 
of  the  urine  injected  was  22°  C.  (71.6°  F.). 

This  animal  has,  therefore,  been  killed  by  the  injection  of 
26.74  cubic  centimetres  of  urine  for  each  kilogramme. 

Urine  of  the  Eight  Hours  of  Sleep. — Quantity,  225  cubic 
centimetres;  density,  1034;  reaction,  acid;  urea,  27.2  grammes 
for  1000,  or,  for  the  whole  of  the  eight  hours  of  sleep,  6.12 
grammes.  This  urine,  neutralized  and  filtered,  is  injected  into  a 
vein  on  the  ear  of  a  rabbit  weighing  1610  grammes.  The  rectal 
temperature  at  the  commencement  of  the  injection  was  40.2°  C. 
(104.4°  F.).  Myosis  commences  after  21  cubic  centimetres  had 
been  injected  ;  it  was  complete  after  33  cubic  centimetres;  after 
26  cubic  centimetres,  agitation  ;  at  46,  clonic  convulsions  ;  at  48, 
strong  convulsions  whilst  in  opisthotonos  ;  death.-  The  heart 
continued  to  beat  but  feebly,  except  the  auricles,  which  contracted 
with  force.  The  pupils  remained  contracted  after  death.  The 
rectal  temperature  at  the  time  of  death  was  39.7°  C.  (103.4°  F.). 
The  temperature  of  the  urine  injected  was  22°  C.  (71.6°  F.).  This 
animal  was,  therefore,' destroyed  by  the  injection  of  4-^~™^=  29-81 


URINE   MOST   TOXIC   IN   EARLY   PART   OF   THE   DAY.  39 

cubic  centimetres  of  urine  for  each  kilogramme.  The  urines  of 
the  sixteen  hours  of  the  wakeful  period  represent  ^g^j  =26.178 
urotoxies,  or,  by  the  hour,  1.G361  ;  or,  by  the  hour  and  per  kilo- 
gramme of  man  who  has  furnished  this  urine,  0.2002.  A  kilo- 
gramme of  man  in  one  hour  of  the  wakeful  state  eliminates, 
therefore,  what  would  kill  20.02  grammes  of  living  material. 

The  urines  of  the  eight  hours  of  sleep  represent  J^  =  7.88336 
urotoxies,  or,  by  the  hour,  0.98542,  and,  by  the  hour  and  for 
each  kilogramme  of  body-weight  of  the  man  who  has  furnished 
the  urine,  0.01206.  A  kilogramme  of  this  man  in  one  hour  of 
sleep  eliminates,  therefore,  what  would  kill  12.06  grammes  of 
living  tissue.  There  results  from  this  that  he  eliminates  what 
would  kill,  in  sixteen  hours  of  the  wakeful  period,  320.32 
grammes,  and  in  eight  hours  of  sleep,  96.48  grammes  of  animal. 
Therefore,  in  twenty-four  hours  he  eliminates  what  would  kill 
416.80  grammes  of  living-  matter.  The  urotoxic  co-efficient  of 
this  man  is  beyond  0.4168.  It  would  require  for  each  kilo- 
gramme of  this  man,  in  order  to  kill  1  kilogramme  of  living 
matter,  two  days,  nine  hours,  and  thirty-five  minutes. 


During  wakefulness  the  greatest  toxicity  belongs  to  the 
first  half  of  the  day  period.  From  a  very  health}7  adult,  I  have 
gathered  separately  the  urines  of  the  three  periods  of  eight 
hours,  representing  the  whole  supply  of  a  day  of  twenty-four 
hours,  waking  and  sleeping.  The  first  two  periods — from  7.15  A.M. 
to  3.15  P.M.,  and  from  3.15  to  11.15  P.M. — represent  the  period  of 
wakefulness.  The  last  period — from  11.15  P.M.  to  7.15  on  the 
following  morning — had  been  devoted  to  sleep.  This  man  fur- 
nished, per  kilogramme  and  for  eveiy  hour,  in  the  first  period 
(morning),  what  would  kill  27.92  grammes  of  living  tissue;  in 
the  second  period  (evening)  what  would  kill  19.58  grammes  ;  and 
in  the  third  period  (sleep)  what  would  kill  11.70  grammes.  The 
proportion  of  the  urinary  toxicity  during  these  three  periods  of 
the  day  has  always  been  sensibly  shown  to  be  the  same ;  it  may 
be  expressed  respectively  by  the  indices  7,  5,  3.  A  graphic 
record  will  allow  of  the  more  easy  penetration  into  the  details 
of  this  study.  I  represent  a  complete  nycthdmere  from  10 
o'clock  at  night  to  10  o'clock  in  the  morning.  The  period  of 
sleep  is  shaded;  it  extends  from  10  o'clock  at  night  to  6  o'clock 
on  the  following  morning :  it  is  thus  eight  hours.  The  period 


40 


LECTURES   ON   AUTO-INTOXICATION. 


of  wakefulness  is  exactly  divided  into  two  equal  parts  of  eight 
hours.  The  one  from  6  o'clock  in  the  morning  to  2  o'clock  in 
the  afternoon  represents  the  morning  period  of  wakefulness  ; 
the  other,  from  2  o'clock  in  the  afternoon  to  10  o'clock  at  night, 
represents  the  evening  period. 

The  horizontal  line  measures  the  duration  of  the  periods  of 
elimination.  The  area  of  the  trapezes  which  rest  upon  this  line 
represents  the  quantity  of  poison  eliminated  in  each  period  ;  the 


/\ 


\ 


\ 


\ 


\ 


\ 


\ 


10  P.M. 


6  A.M. 


MID  DAY  2P.M. 


10  RNI. 


vertical  lines  indicate  by  their  length  the  intensity  or  the  rapidity 
of  the  toxic  elimination  for  every  instant  of  the  day.  We  see 
that  the  minimum  of  this  elimination  is  at  the  moment  when 
man  is  asleep  ;  that  it  is  then  nine  times  less  intense  than  the 
eight  hours  previously,  in  the  middle  of  the  period  of  wakeful- 
ness,  and  five  times  less  than  eight  hours  later  on,  at  the  end 
of  the  period  of  sleep.  We  thus  see  that  from  the  minimum  to 
the  maximum,  during  the  sixteen  hours  which  represent  sleep 
and  the  morning  period  of  wakefulness,  the  intensity  of  the 


URINE  OP   SLEEP   ANTIDOTAL  TO  THAT  PASSED  DURING  THE  DAY.      41 

toxic  elimination  is  produced  with  a  rapidity  twice  greater. 
The  urines  of  the  day  period  do  not  only  differ  from  the 
urines  of  sleep  by  a  toxicity  twice  greater,  but  the  toxicity 
of  these  two  urines  presents  differences  of  a  qualitative 
character.  The  urines  of  sleep  are  always  markedly  con- 
vulsive ;  those  of  the  day  period  are  very  little  or  not  at  all 
convulsive,  but  they  produce  narcosis.  It  is  at  such  a  point 
that  we  are  asked  if  there  is  no  possibility  of  accepting  the  old 
toxic  theoiy  of  sleep, — that, according  to  which,  the  activity  of 
nerve-tissue  is  accompanied  by  the  production  of  a  substance 
from  disassimilation,  whose  action  upon  nerve-cells  would  be 
soporific.  If  this  theor}^  could  be  revived  it  would  be  necessary, 
I  believe,  to  expand  it,  and  to  attribute  to  the  whole  of  the 
economy  the  production  of  nai-cotic  material.  ,  What  is  certain 
is,  that  during  the  day  the  body  forms  a  substance  which,  when 
accumulated,  would  induce  sleep,  and  that  during  sleep  it  elabo- 
rates, instead  of  this  narcotic  substance,  a  convulsive  substance 
which,  when  accumulated,  could  produce  muscular  twitchings 
and  induce  waking. 

The  poisons  of  the  day  period  and  the  poisons  of  sleep  are 
not  only  different  as  regards  intensity  and  qualit}-,  they  are 
antagonistic  :  the  one  is  the  antidote  of  the  other.  If  we  mix 
the  urines  of  the  day  period  and  those  of  the  night  proportion- 
ately to  their  respective  bulks,  the  toxicity  of  the  mixture  is  not 
a  mean — it  is  not  necessarily  intermediate — between  the  toxicity 
of  the  urines  of  the  day  and  those  of  sleep ;  it  may  be  less 
than  the  mean  of  those  urines  which  were  the  least  toxic.  From 
this  we  know  that,  in  order  to  appreciate  the  whole  of  the  toxic 
matter  formed  by  man, — in  order  to  determine  his  urotoxic 
co-efficient, — it  is  well  not  to  attempt  the  toxicity  of  his  urines 
by  employing  a  portion  only  of  the  mixture  of  the  urines 
passed  in  the  twenty-four  hours.  It  is  necessaiy  to  determine 
respective!}'  the  whole  toxicity  of  the  urines  of  the  day  period 
and  the  whole  toxicity  of  the  urines  of  sleep,  then  to  add  the 
two  results.  In  determining  alone  the  toxicit}-  of  the  mixture 
of  the  two  urines  we  would  get  too  small  an  index. 


42  LECTURES   ON   AUTO-INTOXICATION. 

TOXICITY   OF    THE   URINES   OF   THE   DAY   AND   NIGHT    MIXED. 

We  gathered  the  urine  of  twenty-four  hours  passed  by  a 
young,  healthy  man,  aged  28,  weighing  69  kilogrammes.  We 
gathered  separately  the  urine  of  nine  hours  of  sleep — from  10 
o'clock  at  night  to  7  o'clock  in  the  morning — and  the  urine  of 
fifteen  hours  of  wakefulness, — from  7  o'clock  in  the  morning  to 
10  o'clock  at  night. 

Urine  of  Sleep. — Quantity,  450  cubic  centimetres  ;  density, 
1024.  This  urine,  neutralized  and  filtered,  was  injected  into  a 
vein  on  the  ear  of  a  rabbit  weighing  1775  grammes.  Death 
supervened,  after  veiy  slight  convulsions,  when  91  cubic  centi- 
metres had  been  injected.  The  animal  had  thus  received  for 
each  kilogramme  51.26  cubic  centimetres  of  urine. 

Urine  of  the  Day  Period. — Quantity,  720  cubic  centimetres  ; 
density,  1014.  .  This  urine,  neutralized  and  filtered,  was  injected 
into  a  vein  on  the  ear  of  a  rabbit  weighing  1725  grammes. 
Death  supervened,  without  convulsions,  after  45  cubic  centi- 
metres. The  animal  had  thus  received  26.08  cubic  centimetres 
of  urine  for  each  kilogramme. 

Urine  of  Twenty-Four  Hours. — We  mixed  one-third  of  the 
urine  of  sleep  (150  cubic  centimetres^  and  one-third  of  the 
urine  of  the  day  period  (240  cubic  centimetres).  This  mix- 
ture represented  pretty  accurately  the  mixture  of  the  urine  of 
twenty-four  hours.  This  urine,  neutralized  and  filtered,  was  in- 
jected into  a  vein  in  the  ear  of  a  rabbit  weighing  1555  grammes. 
Death  supervened,  without  convulsions,  after  73  cubic  centi- 
metres. The  animal  had  thus  received  for  each  kilogramme 
46.94  cubic  centimetres.  The  urine  of  sleep  represented 
g^g =8.778  urotoxies.  The  urine  passed  during  the  day  repre- 
sented 2^g= 27.607  urotoxies.  The  urine  of  the  twenty-four  hours 
represented,  therefore,  8.778  -f  27.607  =  36.385  urotoxies ;  but  if 
we  wished  to  estimate  this  toxicity  of  the  urine  of  the  twent}'- 
four  hours  by  the  experiment  which  shows  the  toxicity  of  the 
mixture,  we  find  that  this  toxicity  would  only  be  -^^=24.925 
urotoxies.  Thus,  from  the  fact  of  their  being  mixed,  the  urines 
of  the  day  and  of  night  lose  about  one-third  of  their  toxicity. 
From  this  we  ought  strongly  to  conclude  that  man  eliminates 
during  sleep  urine  which  is  parti}1-  antidotal  to  the  urine  of  the 
day,  or  vice  versa.  There  would  thus  be,  therefore,  in  the  dif- 
ferent conditions  of  nerve  function,  different  elaborations  of 
material  capable  of  giving  rise  to  poisons  antagonistic  to  each 
other.  From  this  experiment  we  can  equally  deduce  that  this 
man  was  eliminating  for  each  kilogramme  of  his  own  weight, 
every  hour  during  sleep,  sufficient  to  kill  14.135  grammes  of 


TOXICITY   OF   URINE   REDUCED   BY   MUSCULAR   EXERCISE.          43 

living  matter,  and  during  the  dajr  26.673  grammes  ;  that  during 
the  period  of  twenty -four  hours  (day  and  night)  he  was  eliminat- 
ing sufficient  urinary  poison  to  kill  527  grammes  of  living 
matter.  His  urotoxic  co-efficient  was  therefore  0.527.  To  in- 
toxicate his  weight  of  living  material  he  would  require  forty- 
five  hours  and  twenty-eight  minutes. 


The  toxicity  of  the  urine  of  sleep  being  only  half  of  the 
toxicity  of  the  urine  secreted  during  an  equal  period  of  the  day, 
we  might  think  that  the  urine  of  repose  ought  to  be  less  toxic 
than  the  urine  of  muscular  effort.  But  it  is  the  contrary  which 
is  true.  One  day  of  great  muscular  activity,  spent  in  the  open 
air,  in  the  country,  diminishes  the  toxicity  of  the  twenty -four 
hours  by  one-third,  and  on  that  day  the  toxicity  does  not  dimin- 
ish only  during  the  time  devoted  to  muscular  exercise.  The 
toxicity,  which  diminishes  during  work,  remains  less  during 
the  repose  which  follows  this  work  and  during  the  sleep  which 
succeeds  this  day  of  muscular  activity.  This  fact  has,  I  think, 
an  important  bearing, — it  shows  that  a  large  part  of  the  toxicity 
is  not  attributable  to  the  mineral  substances,  which  certainly  are 
not  diminished  by  the  fact  of  exercise,  and  that  it  depends  upon 
organic  substances  incompletely  oxidized,  whose  toxicity  dimin- 
ishes in  proportion  as  oxidation  is  more  completely  effected. 
We  urge  upon  all,  without  insisting  upon  it  too  much,  the 
interest  which  this  experiment  has  from  a  therapeutical  point 
of  view. 


INFLUENCE   OF   EXERCISE   UPON   THE   TOXICITY   OF   URINE. 

We  gathered  the  urine  of  the  day  and  of  sleep  of  a  man  of 
81,700  kilogrammes,  after  a  day  of  great  bodily  exercise,  spent 
in  the  open  air.  We  have  for  the  day  urine  1070  cubic  centi- 
metres (density,  1020)  and  for  the  urine  of  sleep  243  cubic 
centimetres  (density,  1027).  These  urines  are  acid.  The  urines 
of  the  day  period  were  gathered  on  the  llth  of  October,  from 
1.15  to  10.30  in  the  evening,  and  on  the  12th  of  October,  from 
7  A.M.  to  1.15  P.M.  We  have  therefore  the  urine  secreted  during 
fifteen  and  a  half  hours.  The  urines  of  sleep  were  received  from 
10.30  P.M.  to  7  A.M.,  i.e.,  during  eight  and  a  half  hours. 


44  LECTURES   ON   AUTO-INTOXICATION. 

Into  a  rabbit  weighing  1360  grammes  we  made  an  intra-venous 
injection  of  the  urine  of  the  day  period.  Death  supervened 
after  72  cubic  centimetres,  preceded  by  some  slight  convulsive 
movements.  It  had  received,  for  each  kilogramme  of  its  own 
weight,  52.94  cubic  centimetres.  The  pupils  were  pin-pointed 
at  the  moment  of  death. 

Into  a  rabbit  weighing  1360  grammes  we  injected  the  urine 
of  sleep.  Death  occurred  after  66  cubic  centimetres,  after  severe 
convulsions  and  retroflexion  of  the  body  in  the  form  of  opis- 
thotonos.  It  had  received,  for  each  kilogramme  of  its  weight, 
49.26  grammes.  The  pupils  were  pin-pointed. 

Thus,  during  the  fifteen  hours  and  a  half  of  the  day  period 
1070  cubic  centimetres  of  urine  had  been  secreted.  This  urine 
killed  a  kilogramme  of  rabbit  with  a  dose  of  52.94  cubic  centi- 
metres. Man  during  the  day  has  therefore  secreted  what  would 
kill  ^j°4  kilogrammes,  and  for  each  kilogramme  of  man  and  for 
every  hour  52  79  X$LJ  x  is.5 =0-01596  kilogrammes.  Therefore,  during 
the  day  period  1  kilogramme  of  man  secreted  in  one  hour  what 
would  kill  15.96  grammes  of  rabbit.  During  the  fifteen  and 
one-half  hours  of  the  day  1  kilogramme  of  man  secretes  what 
would  kill  247.38  grammes  of  rabbit. 

During  eight  and  one-half  hours  of  sleep  243  cubic  centi- 
metres of  urine  had  been  secreted.  This  urine  killed  1  kilo- 
gramme of  rabbit  with  a  dose  of  49.26  cubic  centimetres.  Man, 
during  eight  and  one-half  hours  of  sleep,  killed  J^~  kilogrammes, 
and  in  one  hour  492g4^g--;  and  1  kilogramme  of  man  secreted  dur- 
ing one  hour  of  sleep  what  would  kill  ^ex^sxsiT^7'103  grammes 
of  rabbit.  In  eight  hours  and  thii'ty  minutes  of  sleep  1  kilo- 
gramme of  man  secreted  what  would  kill  60.38  grammes  of  rab- 
bit. In  twenty-four  hours  (night  and  day)  1  kilogramme  of  man 
secreted  sufficient  to  kill  247.38  +  60.38  =  307.76  grammes  of 
rabbit. 

The  urotoxic  co-efficient  of  this  man  is,  in  round  figures, 
0.308  :  1  kilogramme  of  man,  in  order  to  secrete  what  would 
kill  1  kilogramme  requires  three  days,  five  hours,  and  fifty-five 
minutes. 

In  equal  time  the  urines  of  the  day  period  have  a  toxicity 
more  than  double  that  of  the  urines  of  sleep.  The  exact  rela- 
tionship for  the  toxicity  of  sleep  compared  to  the  toxicity  of  the 
wakeful  period  is  7.103  : 15.96  =  0.45. 

On  the  whole,  therefore,  the  urotoxic  co-efficient  of  this  man, 
on  a  day  of  heavy  muscular  work  in  the  open  air,  is  0.308.  It 
was,  at  two  periods  of  repose, — the  17th  of  September  and  the 
19th  of  September,— 0.474  and  0.417,  or  a  mean  of  0.445.  The 


THE   TOXICITY   OF   URINE.  45 

relationship  of  the  toxicity  of  the  man  who  works  to  the  toxicity 
of  the  man  in  repose  is  as  0.308:0.445  =  0.692,  or,  in  round 
figures,  0.7.  Muscular  eifort  in  the  open  air  has  therefore  sup- 
pressed j\  of  the  toxicity.  In  this  man  twice,  on  the  occasion 
of  sedentary  work  in  town,  the  toxicity  for  each  kilogramme 
ami  for  every  hour  had  been,  during  the  day,  23.75  grammes  and 
20.62  grammes, — a  mean  of  21.88  grammes, — and  during  sleep 
11.70  grammes  and  12.06  grammes, — a  mean  of  11.88  grammes. 
By  the  fact  of  severe  bodily  exercise  in  the  open  air  it  became, 
during  the  day,  15.96  grammes  and  during  sleep  7.10  grammes. 
The  amount  ^  =  0.720.  The  amount  J— =  0.597. 

Muscular  effort  in  the  open  air  diminished  thus  from  27  for 
every  100  the  toxicity  of  the  da}^,  and  its  influence  extended 
also  to  the  period  of  sleep  which  followed  work,  causing  a  loss 
of  40  in  the  100  to  the  toxicity  of  the  urine  of  sleep.  The 
causes  which  influence  urinary  toxicity  may  therefore  act  during 
the  period  of  their  application  and  also  during  a  long  period 
of  time  after  they  have  ceased  to  exist.  It  is  for  this  reason, 
doubtless,  that  the  morning  period  is  more  toxic  than  that  of 
sleep  and  the  period  of  sleep  less  toxic  than  that  of  the  evening. 


It  is  not  sufficient  to  know  that  the  urines  have  been  rendered 
toxic  by  the  solid  substances  which  they  contain.  What  are 
these  substances?  Amidst  the  different  symptoms  of  urinary 
intoxication,  what  symptoms  belong  to  such  and  such  a  sub- 
stance? Is  there  no  substance  whose  toxicity  is  masked  by  its 
union  with  those  that  are  more  toxic,  these  killing  the  animal 
before  the  first  may  even  have  been  manifested,  and  whose  toxic 
power  would  be  shown  if  they  acted  separately  ?  Is  there  not, 
in  the  pathological  state,  a  diminution  of  normal  toxic  sub- 
stances and  an  increase  of  other  substances  incapable  normally 
of  intoxicating?  There  are  many  other  questions  also  to  which 
we  must  endeavor  to  reply. 

Before  demonstrating  the  degree  of  the  toxicity  of  urine 
taken  in  the  bulk  there  is  only  one  resting-place  for  our  re- 
searches. It  is  necessary  to  dissect,  so  to  speak,  this  mass,  and 
to  operate  upon  it  in  portions,  in  order  to  know  intimately  the 
degree  of  toxicity  of  each  of  the  elements  which  compose  it. 


LECTURE  Y. 
CAUSES  OF  THE  TOXICITY  OF  URINE. 

RSsumfi  of  the  physiological  phenomena  produced  by  the  iutra-venous  injection 

of  normal  urine.     Definition  of  urotoxy  and  the  urotoxic  co-efficient. 

Research  as  to  the  possible  causes  of  the  toxicity  of  urine.     Modification  of 

the  toxicity  of  urine  by  time,  temperature,  exposure  to  air,  fermentation. 

Examination  of  the  constituent  elements  of  urine  from  the  point  of  view  of 
the  part  which  they  may  play  in  its  toxicity.  Water.  Volatile  substances. 
Urea :  Intra-venous  injection  of  urea.  Experiments  of  MM.  Grehant  and 
Quinquaud  by  subcutaneous  injection.  Insignificant  toxicity  of  urea.  Uric 
acid  :  Intra-venous  injection  of  uric  acid.  Feeble  toxicity  of  uric  acid. 
Creatinine  :  Its  toxicity  nil  (Rauke  and  Schiffer).  Odorous  substances. 
Coloring  matters.  Intra-venous  injection  of  colored  urine  and  of  urine 
decolorized  by  means  of  carbon.  Very  important  diminution  of  toxicity  and 
loss  of  the  myotic  power  of  the  urine  after  decoloration.  Alkaloids. Analy- 
sis of  the  toxic  properties  of  urine  by  the  dichotomic  study  of  the  extracts. 
Substances  soluble  in  alcohol.  Substances  insoluble  in  alcohol.  Unequal 
toxicity  and  toxic  modality  different  in  the  two  extracts. Effects  pro- 
duced by  the  substances  soluble  in  alcohol, — somnolence,  coma,  diuresis, 
salivation.  Hypothesis  relative  to  the  appearance  of  this  property,  which  is 

not  possessed  by  urine  naturally. Effects  of  the  substances  insoluble  in 

alcohol.     Convulsions,   myosis,   diminution  of   heat-production.     Unequal 

assimilation  of  the  toxic  power  of  urine  to  that  of  certain   alkaloids. 

Hypothesis  bearing  upon  the  explanation  of  the  physiological  effects  proper 
to  urinary  extracts.  Urea  is,  perhaps,  the  cause  of  the  diuresis.  Loss  of 
the  myotic  power  and  considerable  diminution  of  the  curative  property  after 
carbonization,  which  has  left  in  the  urinary  extracts  nothing  else  than 

mineral  matter. Insufficiency  of  soda  to  produce  the  toxicity  of  urine. 

Toxic  importance  of  potass,  which  partly  contributes  to  the  convulsive 
power  of  urine. 

HAVING  introduced  normal  urine  into  the  veins,  I  have  been 
able  to  demonstrate  that  its  toxic  action  bears  especially  upon 
the  nervous  system,  since  it  paralyzes  movement  without 
destroying  the  contractility  of  muscle,  in  so  far  as  it  allows  the 
heart  to  continue  beating.  Disorders  of  movement  become, 
at  length,  apparent  in  the  pupil,  which  becomes  pin-pointed. 
Myosis  persists  up  to  death,  without  there  being  any  lesion 
of  the  muscles  of  the  iris,  since  the  pupil  generally  dilates  after 
death.  The  movements  of  the  respirator}'  muscles  are  quick- 
ened, those  of  the  locomotor  muscles  weakened.  The  loss  of 
(46) 


DEFINITION   OF   UROTOXIC   CO-EFFICIENT.  47 

the  reflexes  in  the  advanced  phases  of  intoxication,  somno- 
lence, and  coma  still  show  that  the  brunt  is  borne  by  the  ner- 
vous system.  It  is  in  the  same  sense  that  the  disturbances  of 
the  secretory  apparatus  are  to  be  considered, — the  frequent 
emission  of  urine,  the  salivary  hypersecretion,  of  which  we  shall 
speak  soon,  and,  lastly,  the  fall  of  the  temperature  by  diminution 
of  heat-production.  That  is  the  first  fact,  and  it  is  the  funda- 
mental one  in  the  phenomena  of  intoxication. 

Before  going  further,  it  is  necessary  to  establish  a  standard 
to  estimate  whether  an  individual  forms  in  a  given  time  more 
toxic  matter  than  another  individual.  I  have  adopted  the  term 
urotoxy, — toxic  unit,  or  toxicity  of  urines.  The  toxic  unit  is 
the  quantity  of  toxic  matter  capable  of  killing  one  kilogramme 
of  living  animal,  hi  order  to  study  afterward  the  reports  of 
the  various  toxicities,  I  have  established  what  the  urotoxic 
co-efficient  is,  of  which  a  brief  argument  will  explain  the 
necessity.  « 

If  to  kill  a  kilogramme  of  rabbit  30  cubic  centimetres  of  the 
urine  of  Peter  and  60  cubic  centimetres  of  the  urine  of  Paul  are 
necessary,  we  are  first  led  to  believe  that  the  urine  of  Peter  is  the 
more  toxic.  Yet,  we  are  not  altogether  right  in  stating  the  con- 
clusion thus  :  for  if,  in  twenty-four  hours,  Paul  has  secreted  twice 
as  much  urine  as  Peter,  the  loxicit}-  is  equal  in  the  two.  I  go  fur- 
ther :  Two  individuals  eliminate  in  twenty -four  hours  the  same 
quantity  of  urine;  they  kill  with  the  same  dose  a  kilogramme 
of  rabbit ;  it  does  not  necessarily  follow  from  this  that  they 
have  the  same  toxic  power,  for  another  cause  of  variation  111:1  y 
intervene, — the  weight  of  the  individuals;  if  one,  weighing 
less  by  a  half  than  the  other,  makes  the  same  quantity  of  toxic 
material,  he  has  evidently  a  toxic  power  double  that  of  the 
other. 

We  are  thus  led  to  define  the  co-efficient  of  toxicity  as  the 
quantity  of  toxic  matter  which  a  unit  of  weight  produces  in  a 
unit  of  time.  I  will  say,  with  greater  precision,  the  urotoxic 
co-efficient  of  an  individual  is  the  number  of  urotoxies  formed 
in  twenty-four  hours  by  a  kilogramme  of  that  individual. 

These  premises  granted.  \vc  come  now  to  seek  among  the 
constituent  elements  of  urine  for  those  to  which  the  toxicity  of 


48  LECTURES   ON   AUTO-INTOXICATION. 

urine  is  due.  We  discard  at  once  the  idea  that  the  water  is 
toxic.  It  may  be  introduced  with  impunity  into  the  blood  in 
doses  much  larger  than  that  in  which  urine  kills.  Besides,  evapo- 
ration causes  the  urine  to  become  more  toxic.  When,  by  evapo- 
ration, we  reduce  to  one-half  of  its  volume  a  urine  which  kills  1 
kilogramme  of  rabbit  with  a  dose  of  60  cubic  centimetres,  we 
see  that  this  urine  thus  concentrated  kills  with  a  dose  of  30  cubic 
centimetres.  Toxicity  depends,  therefore,  not  on  the  water,  but 
upon  the  substances  which  it  holds  in  solution.  If  evaporation 
is  made  slowly,  we  notice  an  absolute  increase  of  the  toxicity, 
and  no  longer  an  increase  proportional  to  the  degree  of  concen- 
tration. This  can  only  be  explained  by  chemical  changes 
undergone  by  substances  that  are  unstable, — substances  which 
really  do  not  belong  to  the  group  of  minerals.  This  fact,  the 
increase  of  toxicity  by  evaporation,  allows  us  also  to  conclude 
that  the  other  volatile  substances  contained  in  the  urine  are  not 
either  the  cause  of  its  toxicity. 

We  increase  the  toxicity  of  urines  by  leaving  them  for  a  long 
time  to  themselves,  even  if  we  protect  them  from  fermentation. 
Rise  of  temperature,  exposure  to  air  especially,  length  of 
time  in  keeping,  all  modify  their  toxic  power.  Such  a  urine 
which  killed  by  coma  becomes  toxic  with  a  smaller  dose,  but  it 
does  so  by  inducing  convulsions.  If  fermentation  is  set  up  in 
it,  the  toxicity  varies  ;  it  may  be  increased  or  diminished ;  it  is 
in  every  case  changed  by  it.  If  there  is  produced  within  it  car- 
bonate of  ammonia,  we  may  have  the  special  phenomena  wit- 
nessed in  annnonsemia. 

The  increase  of  toxicity  on  keeping  the  urine  already  allows 
us  to  assume  that  it  is  not  the  mineral  substances  which  are  the 
sole  cause  of  the  toxicity,  since  they  are  not  more  abundant  in 
old  urine, — the  potass,  notably,  remains  in  the  same  quantity. 

Before  going  further,  we  may  pass  in  review  some  hypotheses 
which  have  been  enunciated  on  this  subject,  viz.,  the  causes  of 
the  toxicity  of  urine.  Formerly,  for  example,  urea  was  consid- 
ered the  chief  poisonous  agent, — after  the  teaching  of  Wilson. 
The  intra-venous  injection  of  urea,  which  I  have  practiced  a 
great  many  times,  enables  me  to  say  that  we  can  certainly  kill 
with  urea,  as  with  many  other  bodies,  by  modifying  the 


INTRA-VENOUS   INJECTION   OF   UREA.  49 

conditions  of  osmosis :  by  increasing  in  such  proportions  the 
density  of  the  blood  and  the  liquids  of  the  organism  that  we 
ph3'sically  hinder  the  functions  of  nutrition.  But  the  solutions 
of  urea  which  have  not  this  excessive  density  do  not  kill,  or  they 
lead  to  death  only  if  we  have  injected  more  than  122  cubic 
centimetres  of  it  for  each  kilogramme, — a  dose  in  which  pure 
water  kills. 


INTRA-VENOUS  INJECTION  OF  UREA   WITHOUT   MORBID  PHENOMENA. 

October  16,  1884.  Into  a  rabbit  weighing  1690  grammes  we 
inject,  in  ten  minutes,  into  a  vein  on  its  ear,  100  cubic  centi- 
metres of  an  aqueous  solution,  which  contains  exactly  4  grammes 
of  urea.  The  animal  has  thus  received  per  kilogramme  2.366 
grammes  of  urea,  and,  as  this  urea  has  been  introduced  into  its 
blood,  that  makes  30.758  grammes  per  kilogramme  of  blood, — 
about  two  hundred  times  the  normal  quantity  (2.366  X  13  = 
30.758).  The  temperature  at  the  commencement  was  39.7°  C. 
(103.4°  F.) ;  at  the  end  of  the  experiment  it  was  38.8°  C.  (101.8° 
F.).  No  morbid  phenomenon. 

October  25th.     The  animal  is  well. 

October  28th.     It  remains  quite  well. 

The  temperature  of  this  animal  has  fallen  in  ten  minutes  nine- 
tenths  of  a  degree.  The  heat-capacity  of  the  tissues  being  0.8,  the 
animal  has,  therefore,  lost  1690  X  0.8  X  0.9  =  1216.8  calorics. 
On  the  other  hand,  water  injected,  which  was,  at  the  commence- 
ment, of  a  temperature  of  1 6  degrees,  is  heated  to  22.8  degrees, 
and  consequently  has  absorbed  100  X  22.8  =  2280  calorics. 
Water  has,  therefore,  taken  from  the  body  of  the  animal  a 
quantity  of  heat  more  considerable  than  that  which  it  lost  in 
falling  from  39.7  degrees  to  38.8  degrees.  Consequently,  the  in- 
jection has  not  produced  refrigeration  by  impeding  heat-produc- 
tion ;  on  the  contrary,  there  has  been,  during  the  period  of  the 
injection,  an  increase  of  calorification,  since  the  temperature  of 
the  animal  has  remained  higher  than  that  which  it  would  have 
attained  by  the  fact  alone  of  the  refrigeration  due  to  the  injection. 


Fatal  accidents  supervene  only  after  an  injection  containing 
6.31  grammes  of  urea  per  each  kilogramme  of  the  animal,  or  82 
grammes  per  each  kilogramme  of  blood ;  a  supposition  that  there 
is  ten  times  more  urea  than  we  have  found  in  the  blood  of 


'  50  LECTURES   ON    AUTO-INTOXICATION. 

patients  who  have  succumbed,  as  one  would  say,  to  intoxication 
from  this  substance.  It  is  not  admissible  that  urea  is  the  toxic 
agent  of  urine. 


INTRA-VENOUS   INJECTION    OF  A  VERY   LARGE   DOSE  OF  UREA — DEATH. 

October  25,  1884.  We  injected,  in  thirty-five  minutes,  into  a 
vein  in  the  ear  of  a  rabbit  weighing  1790  grammes,  113  cubic 
centimetres  of  an  aqueous  solution  of  urea  at  y1^ — let  us  say  11.3 
grammes  of  urea ;  or,  for  each  kilogramme,  6.31  grammes ; 
or,  for  the  total  mass  of  the  blood  (137  grammes),  11.3  grammes  ; 
or,  for  a  kilogramme  of  blood,  82.03  grammes.  A  fter  injecting  35 
cubic  centimetres,  respiratory  disturbances  were  the  first  to  be 
noticed  ;  respiration  became  slower.  After  58  cubic  centimetres, 
slight  convulsions  and  tremors  renewed  from  time  to  time; 
respiration  was  still  further  slowed.  At  the  end  of  the  injection 
the  animal  was  comatose  ;  it  died  ten  minutes  after  stopping  the 
injection.  At  the  autopsy  we  found  the  blood  of  a  blackish- 
brown  color  ;  nothing  in  the  lungs  ;  almost  no  urine  in  the  blad- 
der. The  quantity  of  urea  which  had  been  introduced  into  the 
blood  was  about  five  hundred  times  greater  than  that  which  the 
blood  contains  in  the  natural  state.  We  might  ask  if  the  accidents 
were  due  to  the  toxicity  of  this  solution  or  to  its  degree  of  con- 
centration, which  might  have  modified  the  physical  conditions 
of  the  blood-globules  or  of  the  cells  of  the  tissues. 


The  experiments  which  I  have  just  cited  appear  to  disagree 
with  the  recent  researches  of  Grdhant  and  Quinquaud.  Death 
supervened,  in  their  experiments,  after  injection  of  6  grammes 
of  urea  for  each  kilogramme  of  animal  ;  but  the  injection  was 
made  into  the  cellular  tissue.  Now,  the  additional  loading  of 
blood  by  urea  could  only  have  been  produced  if  the  whole  dose 
had  penetrated,  all  at  once,  into  the  circulation,  which  is  scarcely 
possible  by  the  subcutaneou's  method.  These  experiments,  inter- 
esting from  an  experimental  point  of  view,  are  without  clinical 
application. 

Six  and  thirty -one  hundredths  grammes  of  urea  are  necessary 
to  kill  1  kilogramme  of  animal ;  to  kill  a  man  of  60  kilogrammes 
it  would  require,  therefore,  that  his  blood  should  retain  more 
than  380  grammes  of  it  at  one  time.  But  1  kilogramme  of  man 


IS   URIC    ACID   TOXIC?  51 

forming,  in  twenty-four  hours,  only  0.33  grammes  of  urea,  or  20 
grammes  for  each  60  kilogrammes,  it  would  require,  in  order 
that  his  death  should  be  due  to  retention  of  urea,  that  he  should 
make  nineteen  times  more  of  it  (32^0  =  19)  in  twenty-four  hours, 
and  that  he  should  not  eliminate  any  of  it  during  that  time ;  or 
that,  making  the  normal  quantity,  he  should  remain  nineteen 
days  without  eliminating  any. 

Some  have  incriminated  uric  acid  as  the  cause  of  the  toxicit y 
of  urine.  But  it  is  made  in  our  bod}7  in  far  too  minute  a 
quantity  (50  to  60  centigrammes  in  twenty-four  hours),  and  the 
gouty  man  can  have  hundreds  of  grammes  of  urate  in  his  de- 
posits without  being  intoxicated  by  it.  Besides,  I  have  been 
able  to  inject  experimentally  into  the  blood  30  centigrammes 
of  uric  acid  for  each  kilogramme  of  animal  without  apparent 
accident ;  I  have  even  been  able  to  inject  as  much  as  64  centi- 
grammes of  uric  acid  in  solution  in  160  cubic  centimetres  of 
water,  to  which  the  necessary  additional  quantity  of  soda  had 
been  added  to  produce  its  solution. 


EXPERIMENT   BEARING   UPON    THE    TOX1CITY   OF   URIC   ACID. 

March  8,  1886.  "We  took  1  gramme  of  uric  acid,  which  we 
dissolved  in  1  cubic  centimetre  of  soda-lye  and  distilled  water. 
We  obtained  250  cubic  centimetres  of  liquid.  We  passed 
through  it  a  current  of  C02  until  it  caused  visible  alterations. 
We  redissolved  with  a  trace  of  soda,  and  filtered.  A  rabbit, 
1560  grammes.  Injection  into  the  auricular  veins  of  250  cubic 
centimetres.  The  animal  received  1  gramme  of  uric  acid,  or, 
per  kilogramme,  0.641  ;  it  received  of  the  liquid  160.35  cubic  cen- 
timetres. It  did  not  die.  Removed,  it  was  only  sick.  Urine 
alkaline,  muddy,  containing  blood.  Heated,  this  urine  became 
slightly  clear.  Albumen  was  precipitated.  We  filtered  it  hot. 
On  cooling,  it  again  became  muddy,  in  a  very  notable  manner, 
and  gave  an  abundant  precipitate  of  basic  unites.  We  filtered. 
Into  the  limpid  liquid  \ve  poured  a  little  acetic  acid.  We  had 
again  an  abundant  precipitate  of  acid  n rates.  The  murexide 
reaction  was  very  distinct.  One  hour  and  three-quarters  after- 
ward  very  strong  convulsions,  which  were  repeated,  until  death, 
— two  hours  and  twenty  minutes  after  the  commencement  of  the 
experiment.  Autopsy  :  numerous  foci  of  pulmonary  apoplexy. 
Nothing  in  the  other  viscera. 


52  LECTURES   ON   AUTO-INTOXICATION. 

The  animal  died  slowly,  and  another  experiment,  performed 
for  comparison,  in  which  I  injected  the  same  quantity  of  water 
and  soda  without  uric  acid,  has  proved  to  me  that  death  was 
alone  due  to  the  excess  of  the  vehicle.  En  resume,  1  kilo- 
gramme of  man  forms,  in  twenty-four  hours,  8  milligrammes  of 
uric  acid.  We  are  far  from  accounting  for,  by  means  of  this 
agent,  the  intoxication  which  10  to  20  cubic  centimetres  of 
urine  produce. 


CONTROL    EXPERIMENT    MADE   WITH    THE    SAME    QUANTITY   OF    SODA- 
LYE   WITHOUT   URIC   ACID. 

March  10th.  We  made  a  solution  of  1  cubic  centimetre  of 
the  same  soda-lye  which  had  served  for  the  previous  experiment 
in  a  quantity  of  distilled  water  sufficient  to  make  250  cubic  cen- 
timetres. We  passed  through  it  a  current  of  C02  until  it  was 
neutralized,  and  we  injected  some  of  this  into  the  veins  of  a 
rabbit  weighing  1460  grammes.  It  received  236  cubic  centi- 
metres of  this  solution,  or  160  cubic  centimetres  of  liquid  per 
kilogramme.  The  injection  was  made  at  4  o'clock;  it  lasted 
fifteen  minutes.  At  7.30  the  urine  was  bloody,  limpid,  acid. 
After  coagulation  of  the  albumen  by  heat,  filtration,  and  cooling, 
no  precipitate  was  produced ;  nor  was  there  produced  .any 
greater  precipitate,  in  this  same  filtered  and  cold  liquid,  when 
we  added  acetic  acid  to  it.  Died  during  the  night.  The  only 
difference  between  this  and  the  last  experiment  is,  that  the  first 
rabbit  received  uric  acid,  whilst  the  second  received  none  at  all. 
The  results  being  the  same  in  the  two  cases,  it  is  clear  that 
death  ought  to  be  attributed  to  this  excessive  quantity,  viz.,  of 
water,  160  cubic  centimetres,  injected  per  kilogramme  of  the 
animal,  and  we  know  that  distilled  water  produces  death  after 
122  cubic  centimetres.  Therefore,  with  64  centigrammes  per 
kilogramme,  uric  acid  is  not  toxic.  I  add  that  we  can  never 
introduce  into  the  veins  of  an  animal  more  uric  acid  than  in  the 
first  experiment,  since  this  dose  of  uric  acid  would  saturate  a 
quantity  of  water  which,  of  itself  alone,  is  toxic. 


We  could  continue  the  demonstration  for  creatinine,  but  the 
experiments,  already  old,  of  Ranke  and  Schiffer  having  estab- 
lished that  it  is  not  toxic,  enable  us  not  to  insist  any  more  upon 
it.  Besides,  we  shall  return,  on  another  occasion,  to  this 
experimental  investigation. 


THE   COLOR   PRINCIPLES   IN   URINE.  53 

I  have  given  some  attention  to  the  part  which  coloring  and 
odoriferous  substances  may  play  in  toxicity.  Evaporation, 
which  drives  off  odoriferous  materials,  increasing  the  toxicity 
of  the  urine,  puts  them  sufficiently  out  of  all  causal  influence. 

Also,  as  regards  the  coloring  principles,  I  have  proceeded  in 
the  following  manner:  I  estimate  the  toxic  power  of  a  urine  by 
a  natural  injection.  I  decolorize  it  by  carbon.  I  inject  this 
decolorized  urine,  and  I  ascertain  that  it  has  lost  nearly  one- 
third  of  its  toxicity.  A  quantity  equal  to  that  which  killed 
only  produces  accidents  that  are  scarcely  perceptible.  It  pro- 
duces particularly  nothing  more  than  pupillary  contraction. 


INTRA-VENOUS   INJECTION   OF   URINE,   COLORED   AND   DECOLORIZED. 

December  4,  1884.  1.  We  injected  65  cubic  centimetres 
of  a  mixture  of  urine,  taken  from  two  healthy  men,  filtered  and 
neutralized,  into  the  auricular  veins  of  a  rabbit  which  weighed 
1650  grammes,  or  39  grammes  for  each  kilogramme. 

We  soon  produced  a  pupillary  contraction,  very  marked,  but 
not  pin-pointed.  The  animal,  after  the  injection,  was  very  much 
depressed.  The  temperature,  previously  39.2°  C.  (102.6°  F.), 
fell  Jo  38.4°  C.  (101.2°  F.),  and  then  to  37.8°  C.  (100°  F.). 

2.  We  injected  102  cubic  centimetres  of  the  same  urine, 
after  having  decolorized  it,  into  a  rabbit  weighing  1670  grammes, 
or  64  grammes  for  each  kilogramme.  The  pupil  was  not  con- 
tracted. The  animal  appeared,  after  the  injection,  much  less 
indisposed  than  that  in  the  previous  experiment.  Temperature 
before,  39.2°  C.  (102.6°  F.) ;  after  it,  38.6°  C.  (101.5°  F.). 


We  are,  therefore,  tempted  to  say  that  one  of  the  toxic 
agents  of  urine  is  a  substance  fixed  by  carbon,  and,  as  the 
coloring  substances  have  this  property,  of  attributing  to  them 
one-third  of  the  toxicity  of  urine;  but  the  conclusion  does  not 
follow,  for,  along  with  the  coloring  material,  other  substances 
may  be  fixed  in  the  carbon. 

One-sixteenth  of  the  potass  is  arrested  by  the  carbon, — 
nearly  the  whole  of  the  alkaloids.  If  decolorized  urine,  which 
has  lost  one-sixteenth  of  its  potass,  has  lost,  at  the  same 
time,  one-third  of  its  toxicity,  then  it  follows  that  in  the  urine 


54  LECTURES  ON   AUTO-INTOXICATION. 

there  is  something  toxic  besides  the  potass.  And  if  the  urine, 
which  has  lost  the  whole  of  its  alkaloids,  still  retains  two- 
thirds  of  its  toxicity,  then  it  follows  that  the  toxicity  does  not 
wholly  reside  in  the  alkaloids.  When  we  exhaust  the  dry 
residue  of  the  urine  by  means  of  alcohol,  we  see  that  the  alco- 
holic extract,  which  really  contains  the  greater  part  of  the  alka- 
loids, is  sensibly  less  toxic  than  the  residue  insoluble  in  alcohol, 
which  ought  to  contain  only  a  few  of  the  alkaloids.  Carbon, 
therefore,  removes  from  urine  the  substance  which  causes  con- 
traction of  the  pupil,  but  not  all  its  toxic  principles. 

Let  us  follow  the  analysis  of  the  toxic  properties  of  urine 
by  means  of  extracts  and  by  adopting  the  dichotomic  method. 
We  shall  evaporate  a  measured  quantity  of  urine  whose  toxicity 
is  known.  The  dry  residue  is  washed,  at  different  times,  in 
absolute  alcohol,  and  then  we  evaporate  to  dryness  the  whole  of 
the  alcoholic  liquids.  We  thus  obtain  two  extracts, — the  one 
containing  substances  soluble  in  alcohol,  the  other  substances 
insoluble  in  alcohol.  These  two  extracts  having  been  dissolved 
in  water,  we  have  two  solutions, — the  one  representing  the  sub- 
stances of  the  urine  which  are  soluble  in  alcohol,  the  other  the 
substances  which  are  insoluble  in  alcohol.  We  gauge  the  tox- 
icity of  these  two  extracts.  We  establish  the  fact  that  both  are 
toxic,  but  in  different  ways. 


INJECTION  INTO   THE  VEINS  OP   A   RABBIT  OP   THE   AQUEOUS  EXTRACT 
OP   NORMAL  URINE   INSOLUBLE   IN   ALCOHOL  ;    DEATH. 

November  11,  1884.  We  take  200  cubic  centimetres  out  of 
the  whole  quantit}1"  of  1300  centimetres  of  normal  urine  passed 
in  twenty-four  hours.  We  evaporate  to  dryness  upon  the  water 
bath  with  chloride  of  calcium  ;  the  residue  has  been  washed  in 
absolute  alcohol ;  all  the  alcoholic  liquids  poured  together, 
filtered,  have  been  distilled  in  the  i*etort  to  dryness ;  the  residue 
.is  the  extract  soluble  in  alcohol.  The  residue  of  the  washings  in 
alcohol  taken  up  by  the  water  represents  the  substances  of  the 
urine  insoluble  in  alcohol.  This  aqueous  solution  of  the  residue 
insoluble  in  alcohol  occupies  a  volume  of  48  cubic  centimetres. 
It  is  introduced  by  intra-venous  injection  into  a  rabbit  weighing 
1610  grammes. 

After  the   entrance  of  12   cubic  centimetres  the  animal  is 


ALCOHOLIC   EXTRACT   OP   NORMAL   URINE.  55 

seized  with  tonic  convulsions  accompanied  by  straightening  of 
the  head.  These  convulsions  rapidly  disappear  after  we  discon- 
tinue the  injections- 

At  the  end  of  42  cubic  centimetres  the  animal  is  seized  with 
a  violent  tonic  convulsion  with  opisthotonos,  vibratory  tremor, 
and  it  dies.  At  no  period  did  it  present  contraction  of  the 
pupil  except  immediately  after  death.  Temperature  before  in. 
jection,  39.2°  C.  (102.6°"F.)  ;  at  the  moment  of  death,  38.6°  C. 
(101.5°  F.).  Symptoms  commenced  on  the  entrance  of  31 
grammes  of  urine  for  each  kilogramme,  and  death  supervened 
when  we  had  injected  the  insoluble  extract  from  108  grammes 
of  urine. 


INTRA- VENOUS  INJECTIONS  OF  THE  ALCOHOLIC  EXTRACT  OF  NORMAL 
URINE;  DEATH. 

November  11,  1884.  Of  200  grammes  of  urine  treated  in 
the  same  way  as  we  have  said  in  the  previous  experiment,  we 
take  the  extract  which  is  soluble  in  alcohol.  This  extract, 
containing  3.90  grammes  of  urea,  is  diluted  with  distilled  water 
in  such  a  manner  as  to  have  a  volume  of  39  cubic  centimetres. 
Urea  is  found  there  to  be  one-tenth.  We  inject  33  cubic  centi- 
metres of  this  solution  into  the  veins  of  a  rabbit  which  weighs 
1870  grammes.  We  see  the  pupil  contract  rapidly;  after  the 
tenth  centimetre  it  is  markedly  contracted.  Starting  from  this 
moment  its  diameter  oscillates,  but  up  to  the  end  of  the  in- 
jection it  remains  smaller  than  in  the  normal  state.  From  this 
point  of  view  this  result  is  exceptional ;  as  a  rule,  the  pupil  is 
contracted  more  by  the  aqueous  than  by  the  alcoholic  extract. 
The  animal  has  no  convulsion,  but  it  falls  gradually  into  a  state 
of  sleepiness ;  remains  unmoved  ;  lies  upon  its  side ;  its  pupil 
gradually  dilates  and  becomes  very  large.  During  this  coma- 
tose period  the  rabbit  salivates  and  urinates  abundantly.  The 
initial  temperature,  which  was  39.4°  C.  (102.9°  F.),  falls  in  a  few 
minutes  (10  or  more)  to  38.8°  C.  (101.8°  F.). 

In  this  experiment,  the  contraction  of  the  pupil  was  mani- 
fested, under  the  influence  of  the  soluble  extract,  from  27 
grammes  of  urine  for  each  kilogramme.  The  last  symptoms 
corresponded  to  the  injection  of  the  soluble  extract,  from  90 
cubic  centimetres  of  urine  for  each  kilogramme. 

November  12th.  The  animal  died  during  the  night.  Nothing 
special  at  the  autopsy. 


The  toxicity  varies  according  to  the  individuals  who  have 


56  LECTURES   ON   AUTO-INTOXICATION. 

furnished  the  urines.  The  toxicity  of  each  of  the  extracts  is 
less  than  that  of  the  whole  urine.  The  manner  in  which  they 
show  their  toxicity  is  different.  Thus,  the  solution  from  the 
dry  extract  of  substances  soluble  in  alcohol  produces  somno- 
lence, deep  coma,  diuresis.  It  does  not  cause  a  marked  dimi- 
nution of  heat-production  (the  small  quantity  of  caloric  lost  is 
only  equivalent  to  the  equalization  of  the  temperature,  which 
takes  place  owing  to  the  quantity  of  liquid  necessary  to  inject 
the  extract)  ;  it  does  not  cause  nryosis,  but  a  new  symptom  is 
caused,  viz.,  salivation, — a  salivation  lasting  three-fourths  of  an 
hour,  at  least  equal  to  that  which  is  produced  by  jaborandi. 

Here,  then,  is  a  fact,  at  first  sight  inexplicable.  How  can  one 
part  of  the  urine  itself  produce  what  the  aggregate  cannot? 
In  order  to  salivate,  it  probably  requires  a  measured  quantity  of 
the  sialogenous  material  soluble  in  alcohol,  and  3ret  there  exists 
an  insufficient  quantity  of  this  sialogenous  matter  in  the  total 
quantity  of  urine  to  cause  death. 

Experimented  upon  in  its  turn  alone,  the  extract  of  sub- 
stances insoluble  in  alcohol  produces  myosis,  like  normal  urine ; 
also  convulsions,  which  we  never  obtain  with  the  extract  of 
substances  soluble  in  alcohol,  but  which  we  obtain  exceptionally 
with  the  aggregate  of  urine.  The  convulsions  are  a  phenome- 
non of  later  development ;  it  requires  a  larger  quantity  of  the 
extract  insoluble  in  alcohol  to  induce  convulsions  than  to  bring 
about  contraction  of  the  pupil.  We  observe,  too,  in  addition, 
diminution  of  temperature;  but  we  neither  obtain  coma,  diuresis, 
nor  salivation.  Thus,  we  are  forced  to  admit  that  there  is  a 
plurality  of  toxic  substances  in  urine.  The  tendency  which  we 
have  to  regard  intoxication  by  means  of  urine  as  similar  to  that 
produced  by  certain  alkaloids  is  not  justified.  Muscarine,  for 
example,  produces  myosis  and  salivation,  but  we  see  these  two 
phenomena  dissociated  when  we  experiment  separately  with  the 
extract  of  substances  soluble  and  with  that  of  others  insoluble 
in  alcohol. 

We  can  still  say  that  coma,  diuresis,  and  salivation  are  not 
produced  by  mineral  substances,  of  Avhich  a  very  small  quantity 
(some  salts  of  potass)  pass  into  the  alcoholic  washing  ;  that 
the  convulsions,  myosis,  and  fall  of  temperature  are  not  attrib- 


PRODUCTION   OP   MY08IS   AND   CONVULSIONS.  57 

utable  to  the  mass  of  organic  substances  which  have  been  caught 
in  the  washing  with  alcohol.  Coma,  which  the  soluble  sub- 
stances in  alcohol  produce,  is  never  caused  by  urea.  This  causes, 
before  death,  no  other  phenomenon  than  diuresis ;  it  does  not 
cause  diminution  of  temperature,  and  does  not  kill,  except  as  we 
have  seen  it  in  enormous  doses  by  preventing  osmosis.  That  is 
what  I  mean.  As  for  replying  to  other  questions,  as  to  the  part 
which  is  played  by  such  or  such  a  body  on  the  production  of 
each  of  the  symptoms  observed  after  the  injection  of  extracts, 
I  cannot. 

I  do  not  know  what  is  the  substance  which,  passing  with  the 
urea  in  the  alcoholic  wash,  produces  coma. 

Diuresis  belongs  to  normal  urine, — to  the  part  of  the  extract 
soluble  in  alcohol, — as  it  does  to  urea,  which,  experimented  upon 
purely  isolated,  is  certainly  diuretic.  I  may  therefore  think 
that  it  is  the  urea  which  is  the  cause  of  the  diuresis. 

Urea  does  not  increase  salivation.  Blood  which  has  a  sial- 
ogenous  power  greater  than  urine  contains  much  less  urea.  I 
do  not  know  what  is  the  substance  which  produces  salivation. 
I  can  only  say  that  we  find  it  in  the  blood,  in  the  muscles,  and 
in  the  liver. 

What  is  it  that  produces  myosis  and  convulsions  ?  Is  it  the 
mineral  substances  ?  We  are  tempted  to  say  that  it  is.  Decol- 
orized urine,  however,  which  has  lost  little  of  its  mineral  sub- 
stance no  longer  causes  convulsions  nor  myosis.  Experiment- 
ally, after  carbonization  of  the  extract,  the  dissolved  residue, 
which  no  longer  contains  anything  but  mineral  substances,  does 
not  produce  convulsions  or  myosis.  Myosis  is  never  produced  ; 
but  if  we  inject  more  mineral  material  than  the  mass  of  urine 
contains  which  has  killed  without  convulsions,  we  may  induce 
death,  and  then  it  is  always  preceded  by  convulsions. 

We  might  raise  as  an  objection  to  this  experiment  that  car- 
bonization has  caused  to  become  volatile  certain  mineral  salts,  or 
that  it  has  changed  their  chemical  condition.  But  carbonization 
is  not  calcination  ;  besides,  in  experimenting  with  fixed  bases, — 
soda  and  potass, — we  can  appreciate  the  direct  etfects  of  these 
substances. 

Soda  is  convulsion-producing.    Neutralized  by  carbonic  acid, 


58  LECTURES   ON   AUTO-INTOXICATION. 

— that  is  to  say,  under  the  form  of  bicarbonate  of  soda  in  dilute 
solution, — it  induces  haemorrhages,  by  rendering  the  blood  more 
fluid.  As  Magendie  said,  and  as  I  established  again  experi- 
mentally in  1869,  severe  convulsions  appear  with  a  dose  of  1.20 
grammes  for  each  kilogramme  of  animal,  and  death  at  2.50 
grammes.  But  urine  contains  at  the  most  8  grammes  of  salts 
of  soda  per  litre, — that  is  to  say,  48  centigrammes  for  60  cubic 
centimetres  of  urine.  Urine  contains,  therefore,  scarcely  half 
of  the  soda  capable  of  producing  convulsions,  and  one-fourth 
of  that  capable  of  inducing  death. 

Potass  is  infinitely  more  toxic.  Bicarbonate  of  potass  causes 
death,  with  violent  convulsions,  in  small  doses  of  5  centigrammes 
for  each  kilogramme  of  animal,  and  convulsions  come  on  after 
a  dose  of  3  centigrammes.  Potass  is  forty-four  times  more 
toxic  than  soda;  but  if  AYC  find  2  grammes  of  salts  of  potass 
per  litre  of  urine, — that  is,  12  centigrammes  for  60  cubic  centi- 
metres,— it  is  not  in  the  form  of  potassium  bicarbonate,  but  as 
chloride  sulphate  and  other  salts  of  potassium,  which  are  less 
toxic,  and  whose  degree  of  toxicity  we  shall  investigate  later  on. 
We  can,  nevertheless,  admit  that  for  potass  there  is  a  limit  as  to 
toxicity.  If  there  arise  an  excess  of  it  in  the  blood,  even  little, 
convulsions  and  death  may  be  the  consequence  of  it. 

When  we  inject  a  solution  of  mineral  substances,  obtained 
not  by  carbonization  but  by  calcination,  we  sometimes  observe 
this  paradoxical  result :  in  order  to  kill,  it  requires  less  of  these 
substances  than  there  is  in  the  quantity  of  normal  urine,  the 
injection  of  which  produces  death.  That  explains,  I  think,  how 
calcination  has  transformed  into  carbonates  a  part  of  the  alka- 
line salts ;  and,  as  regards  the  same  quantity  of  soda  or  of 
potass,  the  carbonates  of  these  bases  are  two  or  three  times 
stronger  than  the  chlorides,  sulphates,  or  phosphates. 

Ammonia  is  toxic, — less  than  potass,  but  more  than  soda. 
At  15  centigrammes  per  kilogramme,  ammonia,  regarded  as  an 
anhydrous  substance,  and  neutralized  in  water  by  means  of  car- 
bonic acid,  produces  convulsions  and  then  death.  But  normal 
urine  only  contains  doubtful  quantities  of  ammonia. 

In  short,  amongst  the  mineral  matters,  potass  is  the  one 
thing  alone  which,  perhaps,  makes  itself  felt  in  the  toxic  totality. 


POTASS   A   TOXIC   ELEMENT.  59 

I  have  finished  telling  you  what  I  know  of  the  part  which 
belongs  to  each  of  these  substances  in  the  toxicity  of  urines 
which  we  suspect.  I'  have  said  what  I  know,  but  not  what  we 
ought  to  know.  Analj-sis  and  the  isolation  of  various  toxic 
principles  from  the  urine  ought  certainly  in  the  future  to  be 
carried  further. 


LECTURE   VI. 

Toxic  PRINCIPLES  IN  URINE — THE  PART  THEY  PLAY  IN 
PRODUCING  UREMIA. 

Recapitulation  of  the  seven  toxic  substances  found  in  normal  urine.  Diuretic 
substance,  which  is  in  reality  urea.  Useful  function  of  urea.  Narcotic  sub- 
stance. Sialogenous  substance,  whose  action  is  not  shown  after  the  injection 
of  normal  urine,  because  it  is  found  to  be  masked  by  more  toxic  substances. 
Two  substances  which  cause  convulsions.  Organic  convulsive  substance, 
whose  physiological  action  is  habitually  masked  by  its  association  with  a 
narcotic  substance.  Substance  which  contracts  the  pupil.  Heat-reducing 
substance,  acting  through  diminished  heat  formation.  Mineral  convulsive 
material :  potass.  Neutralization  of  its  action  by  a  substance  which  produces 
narcosis.  Analysis  of  the  cause  of  death  after  double  nephrectomy. Com- 
parison of  the  clinical  symptoms  of  uraemia  and  of  the  physiological  proper- 
ties of  the  toxic  substances  of  urine.  Coma  or  convulsions  :  causes  of  the 
comatose  form,  convulsive  or  mixed.  Dyspnoea.  Myosis  :  importance  of 
this  sign,  from  a  diagnostic  point  of  view,  as  regards  uraemia.  Salivation. 

Hypothermia. Diminution  of  the  urinary  secretion  when  urea   ceases 

to  be  formed  or  is  retained  in  the  organism.     Re-instatement  of  the  urea. 
Additional  toxic  substances  of  urine,  salts  of  soda,  alkaloids. 

AFTER  having  concluded  the  physiological  analysis  of  the 
toxic  principles  of  urine,  if  we  recapitulate  the  substances  which 
we  have  disassociated  we  find  there  are  seven  of  them.  There 
is,  first,  a  diuretic  substance, — fixed,  of  organic  nature,  since  it  is 
destroyed  by  heat.  It  is  not  fixed  by  carbon  ;  it  is  soluble  in 
alcohol,  and  we  find  it  mixed  in  the  alcoholic  extract  along  with 
other  substances  which  have  different  properties.  This  sub- 
stance possesses,  besides  the  preceding  characters,  the  property 
which  experimentation  allows  us  to  attribute  to  urea, — that  of 
augmenting  the  quantity  of  urine.  We  have  thus  the  right  to 
say  that  this  diuretic  substance  contained  in  normal  urine  is  no 
other  than  urea.  Urea  in  this  way,  although  it  is  a  product  of 
disassimilation,  plays  a  useful  role  in  the  economy :  it  possesses 
the  property  of  forcing  the  renal  barrier;  of  removing,  whilst 
making  its  own  escape  from  the  organism,  both  the  water  in 
which  it  is  itself  dissolved  and  other  toxic  matters  which  are 
united  with  it.  Without  doubt,  urea  is  itself  toxic.  It  is  like 
(60) 


TOXICITY   OF   UREA.  61 

ever}*  other  substance, — like  water  itself,  which,  introduced  in 
sufficient  quantity  into  the  organism,  can  kill. 

But  in  what  dose  is  urea  toxic?  An  enormous  dose?  It  is 
necessary  to  fetter  the  functions  of  the  organism ;  to  introduce 
into  the  veins  5.5  grammes  to  6.3  grammes  of  urea  per  kilo- 
gramme of  the  weight  of  the  animal.  In  the  experiments  in 
which  we  have  killed  rabbits  b}'  the  injection  of  urea  we  required 
from  71.5  grammes  to  82  grammes  for  1000  grammes  of  blood. 
There  are,  therefore,  few  bodies  in  the  organism  so  feebly  toxic 
as  urea,  if  we  except  albumen  and  the  water  which  naturally 
exists  in  the  blood.  Sugar  is  more  toxic  ;  we  can,  experi- 
mentally, scarcely  introduce  more  than  5  grammes  per  kilo- 
gramme, or  65  grammes  per  litre  of  blood.  Yet,  in  order  to  kill 
immediately  by  intra-venous  injection  of  a  sucrose  liquid,  we 
must  introduce  almost  10  grammes  per  kilogramme  of  the  rabbit, 
or  130  grammes  per  kilogramme  of  blood.  In  pathological  blood 
there  may  be  8  grammes  of  sugar  per  kilogramme  of  blood  ;  but 
in  pathological  blood  urea  has  been  found  in  quantity  at  least 
equal.  Amongst  the  mineral  substances  the  most  inoffensive 
elements,  even  bicarbonate  of  soda,  which  we  so  readily  pre- 
scribe therapeuticall}',  cannot  be  injected  in  a  larger  dose  than 
2.50  grammes  per  kilogramme  of  animal,  32  grammes  per  kilo- 
gramme of  blood.  In  order  to  kill  1  kilogramme  of  a  rabbit  5 
grammes  of  chloride  of  sodium  are  sufficient;  6  grammes  of 
phosphate  of  soda;  9  grammes  of  sulphate  of  soda.  Urea  has 
almost  the  toxicity  of  the  most  inoffensive  salts. 

We  might  say  that  urea,  by  inducing  renal  secretion,  is 
eliminated  quickly,  and  that  this  rapid  elimination  protects  us 
against  its  toxic  influence.  The  reply  to  this  objection  is  found  in 
nephrectoni}'  followed  by  injection  of  urea,  an  experiment  already 
performed  by  Bernard.  In  one  of  my  experiments  of  the  intra- 
venous injection  of  urea  in  the  rabbit,  the  animal  was  dead  after 
the  introduction  of  6.31  grammes  of  urea  per  kilogramme.  It 
had  not  urinated  during  the  experiment,  and  at  the  autopsy  the 
bladder  was  empty.  Besides,  however  active  the  renal  circulation 
may  be,  the  rapidity  with  which  the  quantity  of  urea  that  we  in- 
ject is  found,  as  having  entered  into  the  circulation  by  our 
method  of  intra-veiious  injection,  is  such  that  the  elimination 


62  LECTURES   ON    AUTO-INTOXICATION. 

has  not  time  to  occur,  and  the  physiological  properties  of  urea 
show  themselves  immediately. 

We  have  afterward  met  with  in  the  urine  a  substance  truly 
toxic.  It  is  narcotic;  it  is  fixed,  of  organic  nature  ;  is  not  fixed  by 
carbon  ;  is  soluble  in  alcohol,  and  is  found  in  the  alcoholic  extract 
with  urea  and  other  substances.  Certainly  it  is  not  urea,  since  in 
the  experiments  made  with  urea  we  do  not  see  it  produce  narcosis. 
This  narcotic  substance  which  the  urine  contains  I  cannot  name 
to  you  ;  a  chemical  analysis  of  it  has  not  been  made.  We  can  only 
designate  it  by  enumerating  some  of  the  physical,  chemical,  and 
physiological  characters  which  we  have  found  belonging  to  it. 

A  third  substance  is  sialogenous;  it  produces  salivation.  Its 
presence  in  urine  could  not  be  suspected  from  the  injection  of 
normal  urine ;  the  total  quantity  of  urine  sufficient  to  kill  does 
not  contain  this  sialogenous  substance  in  sufficient  quantity  in 
order  to  produce  its  physiological  effect.  We  only  see  saliva- 
tion appear  after  the  injection  of  urine  deprived  of  a  part  of 
its  toxic  substances,  of  those  which  lead  up  to  death  too  rapidly 
without  giving  time  for  the  sialogenous  substance  to  show  its 
properties.  This  substance  is  stable,  organic,  not  fixed  by 
carbon,  soluble  in  alcohol  like  the  preceding,  but  it  is  distinct 
from  urea  as  well  as  from  the  narcotic  substance.  It  certainly 
comes  from  the  body  like  urea,  for  we  find  it  in  the  blood,  the 
liver,  and  the  muscles  in  a  greater  quantity  than  in  urine,  but 
urea  is  only  found  in  minimum  quantity  in  the  extracts  of  blood 
and  muscle.  We  do  not  yet  know  its  name  or  its  chemical 
nature ;  we  are  only  on  the  threshold  of  discoveries  which  yet 
remain  to  be  made  in  the  chemical  analysis  of  urine ;  we  have 
only  succeeded  so  far  in  dividing  urine  into  several  parts,  in 
each  of  which  one  day  we  shall  isolate  those  bodies  of  which  we 
are  only  able  to  suspect  the  presence. 

We  find  in  urine  two  substances  endowed  with  the  property  of 
causing  convulsions:  one  is  fixed,  stable,  organic,  since  it  is  de- 
stroyed by  carbonization,  and  yet  it  is  retained  by  carbon  ;  it 
is,  therefore,  not  mineral ;  it  is  insoluble  in  alcohol ;  it  might 
belong  to  the  group  of  coloring  substances,  from  the  manner  in 
which  it  behaves ;  it  is  really  an  alkaloid,  since  it  is  insoluble  in 
alcohol  either  in  the  form  of  a  salt  or  a  base.  This  organic 


SUBSTANCES   WHICH  CAUSE   CONVULSIONS   AND   MYOSIS.  63 

matter  which  determines  convulsions  is  found  in  less  quantity  in 
the  urine  of  the  day  period  than  is  the  narcotic  material,  but  it 
is  of  less  physiological  activity ;  and  if  injections  of  normal 
urine  do  not  often  produce  convulsions,  it  is  probablj'  because 
the  narcotic  substance  kills  the  animal  before  the  convulsive 
substance  can  have  exhibited  its  properties.  In  order  to 
produce  convulsions  it  is  necessary  to  remove  first  from  the 
urine  the  poison  which  kills  rapidly.  Of  this  convulsive  sub- 
stance we  also  do  not  know  the  name.  Then  there  is  a  substance 
which  causes  contraction  of  the  pupil ;  fixed,  organic,  attaching 
itself  to  carbon  ;  non-mineral ;  consequently  it  is  comparable  in 
certain  respects  to  the  substance  which  induces  convulsions. 
We  might  suppose  that  it  is  mixed  with  it ;  that  is  to  say,  that 
one  substance  might  be  endowed  with  the  two  properties ;  we 
might  also  ask  if  it  is  not  a  coloring  substance  or  an  alkaloid. 
A  coloring  substance  ?  It  is  possible.  Alkaloid  ?  Probably  not, 
for  the  same  reason  that  we  have  given  when  speaking  of  the 
convulsive  substance.  It  is  not  probable  that  it  is  mixed  with 
the  preceding,  for  all  normal  urines  contract  the  pupil,  but  it  is 
very  few  of  them  which  induce  convulsions.  It  would  be 
necessary  to  admit  that  the  substance  which  convulses  the 
sphincter  iridis  is  more  energetic  than  that  which  brings  on 
general  convulsions. 

Urine  produces  pupillary  contraction  in  small  doses,  from 
10  cubic  centimetres,  and  in  general  it  causes  death  without  con- 
vulsion in  doses  of  from  30  to  50  cubic  centimetres.  We  ought, 
with  cpnvulsive  urines,  at  60  cubic  centimetres  to  see  imme- 
diately happen  contraction  of  the  iris,  whilst  the  phenomenon 
shows  itself  slowly  enough.  The  separation  of  these  two  physio- 
logical effects  shows  that  they  belong  to  two  different  substances. 
We  cannot  give,  any  more  than  for  other  toxic  substances,  the 
name  of  that  which  causes  contraction  of  the  pupil. 

We  have  met  with  in  the  urine  a  substance  which  reduces 
heat.  It  lowers  the  temperature  by  diminishing  heat-produc- 
tion, and  not  only  like  every  cold  liquid,  which,  introduced  into 
the  organism,  subtracts  from  it  a  certain  number  of  calorics  in 
order  to  put  it  into  equilibrium  with  its  own  temperature ;  for 
when  we  inject  a  cold  liquid  into  the  circulation,  we  only  pro- 


64  LECTURES   ON   AUTO-INTOXICATION. 

duce  a  very  slight  fall  of  the  temperature  of  the  body ;  in  real- 
ity, in  this  case,  we  stimulate  calorification  exactly  as  is  done 
by  the  external  application  of  cold :  the  organism  tends  to 
remake,  by  an  acceleration  of  internal  combustions,  the  calorics 
which  we  have  removed  from  it,  and  it  restores  really  a  part  of 
it.  After  the  injections  of  urine,  on  the  contrary,  the  animal  is 
colder, — not  only  as  after  every  injection  of  cold  water,  because 
the  organism  puts  itself  into  an  equilibrium  of  temperature 
with  the  liquid  injected,  but  because  the  organism  loses  a  part 
of  its  heat-producing  power.  Each  unit  of  weight  of  the  body 
forms  in  a  given  time  fewer  calorics  than  in  the  normal  state. 

The  heat-lowering  substance  is  fixed,  organic.  Ammonia 
also  possesses  the  property  of  reducing  temperature ;  but  that 
of  which  we  speak  fixes  itself  on  carbon,  and  is  not,  therefore, 
a  mineral.  It  is  insoluble  in  alcohol,  like  the  preceding.  It  maj' 
be  a  color-substance ;  it  is  certainly  not  the  same  material  as  that 
which  produces  convulsions,  for  we  do  not  observe  any  propor- 
tion between  the  hypotfaonoic  effect  and  the  convulsive, — no 
more  than  between  these  and  the  pupillary  contraction.  It  is, 
therefore,  a  substance  with  an  individuality  of  its  own. 

In  short,  we  find  in  urine  another  convulsive  substance, 
fixed,  inorganic.  It  is,  briefly,  potass,  whose  toxic  and  convul- 
sive properties  we  have  known  for  a  long  time.  Nevertheless, 
we  cannot  attribute  to  it  alone  the  convulsions  which  the  in- 
jections of  urine  produce,  for,  in  order  to  inject  potass  in  a 
toxic  dose,  very  much  larger  quantities  of  urine  would  require 
to  be  injected.  If  we  could  get  rid  of,  by  means  of  carbon, 
a  convulsive  substance  which  kills  too  rapidly,  we  might  see 
convulsions  come  on  due  to  potass.  If,  in  dealing  with,  the 
extract  which  at  one  and  the  same  time  contains  both  the 
convulsive  organic  substance  and  potass,  we  destroy,  by  means 
of  heat,  the  organic  matter ;  convulsions  are  still  produced, 
but  there  must  be,  occasionally,  a  double  quantity  of  urine. 
Alcohol,  it  is  true,  has  removed  a  part  of  the  potass ;  some- 
times, however,  in  order  to  kill  in  convulsions,  it  is  sufficient 
to  inject  the  mineral  substances  taken  from  a  quantity  of  urine 
less  than  the  normal  quantity  of  urine  which  produces  death 
without  convulsions.  This  paradoxical  result,  which  I  have 


TWO   SUBSTANCES   CAUSE   CONVULSIONS.  65 

already  mentioned  and  attempted  the  interpretation  of  in  the 
last  lecture,  might  also  be  explained  by  the  antagonistic  action 
of  certain  organic  substances  which  correct  the  convulsive  action 
of  potass. 

En  resume,  there  are  two  substances  in  urine  which  induce 
convulsions, — one,  organic,  producing  a  rapid  effect,  which  kills 
before  the  convulsions  caused  by  potass  could  have  been 
produced;  the  other,  potass,  a  salt  of  which,  viz.,  chloride  of 
potassium,  is  convulsive  and  toxic  at  18  centigrammes  for  every 
kilogramme  of  the  animal.  This  neutralization  of  one  toxic 
substance  through  admixture  with  another  is  seen  under  many 
circumstances.  Atropine  can  neutralize  the  physiological  action 
of  pilocarpine.  In  the  injections  of  normal  urine  the  convul- 
sive properties  of  the  salts  of  potass  are  neutralized  by  their 
mixture  with  a  substance  which  produces  narcosis  and  coma. 
Thus,  nrines  contain  the  antidotes  to  certain  of  their  own 
poisons. 

When  we  destroy  the  extract  of  urine  by  heat,  the  convulsive 
action  of  the  residue  is,  perhaps,  weakened  by  the  volatilization 
of  a  part  of  the  potass.  In  every  case,  there  is  good  cause 
for  taking  into  account  potass  in  the  toxic  phenomena  con- 
sequent upon  the  retention  of  substances  which  ought  to  be 
eliminated  by  the  urine ;  for  the  accumulation  of  potass  may 
go  on  more  rapidly  than  that  of  other  substances  coming  from 
the  organism.  If,  in  consequence  of  failure  in  the  elimination 
of  the  substance  in  urine  which  reduces  calorification,  disas- 
similation  of  the  tissues  diminishes,  the  potass  which  con- 
tinues to  be  introduced  into  the  organism  b}'  the  food  and  drink 
may  be  soon  found  to  be  in  a  predominating  proportion,  and 
may  induce  convulsions,  which  is  one  of  its  properties.  Thus, 
with  urea,  the  urine  contains  seven  toxic  substances.  To  be 
exact,  it  would  be  necessary  to  say  that  everything  in  the  urine 
is  toxic, — evei-y thing  contained  therein,  even  water  and  soda, — 
but  I  say  seven,  including  therein  only  the  substances  which  are 
toxic  in  doses  in  which  normal  urine  is  experimentally  toxic. 
In  this  analysis,  long  as  it  may  seem,  of  the  toxicity  of  urines, 
it  is  still  only^vn  outline,  which  chemistry,  without  doubt,  will 
finish,  by  the  aid  of  improved  methods. 


66  LECTURES  ON   AUTO-INTOXICATION. 

It  is  sufficient  for  us,  for  the  moment,  to  have  demonstrated 
experimentally  that  urine  removes  poisons  from  the  body  ;  that 
the  kidney  plaj'S  a  useful  role ;  that  it  is  a  good  emunctory ; 
that  its  suppression  would  be  fatalty  hurtful  to  the  economy, — 
an  old  opinion,  which  is  sanctioned  by  the  name  of  emunc- 
tory. Is  it  the  case,  however,  that  suppression  of  the  urinary 
secretion  is  fatally  dangerous?  At  first,  proof  appears  to 
arise  from  the  fact  that  death  invariably  follows  double  ne- 
phrectomy.  We  say  that  death  is,  then  (in  such),  the  result 
of  an  auto-intoxication.  But  the  argument  is  not  indisputable. 
There  are  many  other  modes  of  death  besides  nephrectomy. 
Might  it  not  be  that  death  was  afterward  caused  by  the  want 
of  elimination  of  water,  or  that  the  reflex  paths  of  the  renal 
plexus,  being  irritated,  produce,  in  consequence  of  changes 
in  the  elaboration  of  the  matter  of  the  body,  transformation  of 
certain  organic  compounds,  like  that  of  urea,  into  carbonate  of 
ammonia,  or  that  new  compounds  were  formed  by  reaction,  and 
in  an  indirect  manner?  To  this,  as  an  objection,  it  has  been 
replied  that  after  nephrectomy  we  neither  see  produced  anasarca 
nor  oedema  of  the  brain ;  that  we  do  not  find  in  the  organism 
more  carbonate  of  ammonia ;  that  the  reflexes  could  not  of 
themselves  have  done  so,  since  we  have  suppressed,  in  certain 
experiments,  the  track  along  which  they  have  passed.  What- 
ever the  worth  of  this  argument  may  be,  in  order  to  clear  away 
the  last  point  which  separates  us  from  certaint}',  it  is  necessary 
that  we  should  find  again  in  the  symptoms  of  uraemia  the  physio- 
logical characters  proper  to  the  toxic  matters  of  the  urine.  Does 
the  clinical  picture  of  uraemia  supply  this  want  ?  (Edema  may 
be  present,  but  it  is  rare. 

We  observe  coma  and  convulsions, — sometimes  one,  some- 
times the  other  of  these  symptoms, — probably  because  the 
kidney  does  not  offer  the  same  resistance  to  all  the  substances 
which  pass  through  it.  In  interstitial  and  in  parenchymatous 
nephritis  it  does  not  always  retain  the  same  substances, — salts, 
extractives,  etc.  ;  from  these  differences  in  its  permeability  for 
such  and  such  a  toxic  substance  might  well  result  the  predomi- 
nance of  comatose  or  of  convulsive  uraemia,  or  one  of  a  mixed 
nature. 


UREMIA   AND   ITS   MANIFESTATIONS.  67 

Dyspnoea  is  present  in  uraemia,  with  diminution  of  the  range 
of  respiratory  movements.  I  may  point  to  myosis  as  one  of 
the  constant  characters  of  uraemia.  In  the  evolution  of  chol- 
eraic phenomena  we  see  in  succession  the  intoxication  proper  to 
cholera  and  unemic  intoxication.  When  this  latter  arises  myo- 
sis appears.  All  those  suffering  from  the  anuria  of  cholera  have 
the  pupil  contracted.  Myosis  has  already  been  pointed  out  by 
Roberts  as  one  of  the  signs  of  anuria. 

Salivation  has  been  observed  by  A.  Robin  in  uraemia.  A  sub- 
normal temperature  has  been  regarded  as  one  of  the  commonest 
manifestations.  What  is  awanting  in  the  picture  of  uraemia,  in 
order  that  it  may  be  identical  with  that  which  poisoning  by  means 
of  the  toxic  principles  of  urine  produces  ?  There  is  only  awanting 
the  abundance  of  the  secretion  induced  by  the  great  elimination 
of  urea,  for  it  is  urea  which  is  diuretic.  Urea  upon  a  diseased 
kidney  can  no  longer  exercise  a  beneficent  influence.  Besides, 
when  urea  is  no  longer  formed  in  the  body,  the  kidney — even 
when  normal — ceases  to  show  its  functional  activity.  In  hepatic 
uraemia,  when  the  liver  no  longer  forms  urea;  although  the  kid- 
ney remains  normal,  we  often  see  the  same  symptoms  arise  as  if 
it  had  become  impermeable.  We  are  thus  led  to  this  unexpected 
conclusion,  that  the  substance  urea,  which  has  been  for  such  a  long 
time  the  scare-crow  of  physicians,  is  especially  injurious  when  it 
is  deficient.  In  the  enumeration  of  the  toxic  substances  of  urine, 
I  have  neglected  some,  either  because  they  are  really  scarcel}' 
toxic,  like  the  salts  of  soda,  or  because  they  are  only  found  in 
the  urine  in  very  small  quantity.  Such  are  the  urinary  alkaloids 
b}'  which  we  have  only  recently  tried  to  explain  the  toxic  acci- 
dents of  diseases  in  general,  but  which,  although  numerous  in 
both  the  normal  and  pathological  state,  have  not  until  now  been 
proved,  from  our  point  of  view  of  the  toxicity  of  normal  urine. 
They  belong,  without  doubt,  to  the  number  of  those  indeter- 
minate and  unknown  substances  of  which  I  have  attempted  to 
give  a  physiological  analysis.  M.  Gabriel  Pouchet  said  in  1880 
that  they  were  toxic  :  he  saw  them  produce,  in  animals, muscular 
weakness,  stupor,  convulsions,  then  death,  with  the  heart  in 
diastole.  But  he  had  operated  with  the  ethereal  extract  of  large 
quantities  of  urine,  and  upon  very  small  animals, 


68  LECTURES   ON   AUTO-INTOXICATION. 

Confining  ourselves  to  the  limit  of  things  applicable  to 
pathology,  if,  instead  of  attending  to  the  frog,  we  operate  upon 
the  rabbit,  we  find  that  the  toxicity  of  these  alkaloids  is  nil  in 
the  doses  in  which  they  are  extracted  from  quantities  of  urine 
capable  of  bearing  some  comparison  to  man.  The  quantity  of 
urine  which  would  be  capable  of  killing  a  man  does  not  give  off 
to  the  ether  sufficient  alkaloid  to  kill  a  rabbit. 

I  believe  that  I  have  not  neglected,  in  this  analysis  of  the 
toxicity  of  urines,  anything  but  which  was  worthy  of  neglect. 
The  alkaloids  of  the  urine  are  interesting  from  the  physiological 
point  of  view  of  their  origin,  but  they  do  not  seem  to  have  the 
power  of  explaining  by  themselves  alone  the  intoxication  arising 
from  normal  urines. 


LECTURE   VII. 

ORIGIN  OF  THE  Toxic  SUBSTANCES  OF  URINE — TOXICITT  OF 
THE  BLOOD  AND  TISSUES. 

The  blood  is  unceasingly  traversed  by  a  current  containing  toxic  material  which, 
coming  from  the  organs,  is  continually  being  eliminated  by  the  emunctories ; 
but  blood  ought  never  to  contain  at  any  time,  in  the  normal  state,  more  than 
an  infinitesimal  quantity  of  poison.  Estimation  of  the  toxicity  of  blood  by 
experimentation  and  calculation.  Toxicity  of  the  liquor  sanguinis.  Com- 
parative injections  of  blood  into  animals  of  the  same  and  different  species. 
Injections  of  blood-serum,  of  distilled  water,  and  of  artificial  serum.  Increase 
of  the  toxicity  of  blood  by  the  destruction  of  globules,  which  disengage 

potass.     Toxicity  of  aqueous  and  alcoholic  extracts  of  blood. Toxicity  of 

the  tissues  and  organs  ;  difficulty  of  this  research. Toxicity  of  the  extract 

of  meat  due  to  the  presence  of  mineral  salts,  'such  as  potass ;  and  to  organic 
substances,  such  as  creatiuin.  Intra-venous  injections  of  extracts  of  muscle. 
Aqueous  extracts  of  muscle  produce  convulsions,  with  the  exception  of 
myosis.  The  extract  of  muscle,  deprived  of  the  potass  which  it  contains, 

does  not  produce  any  accident. Toxicity  of  an  extract  of  liver.     Toxicity 

of  bile.  Various  explanations  offered.  The  toxicity  of  biliary  salts  is  less 
than  one  would  have  believed  It ;  they  probably  act  only  indirectly  in  destroy- 
ing anatomical  elements  and  in  setting  at  liberty  mineral  or  organic  products 
derived  from  cellular  disintegration.  Cholesterin  possesses  only  an  insig- 
nificant toxicity.  The  coloring  matters  ought  to  play  a  very  important  role 
in  the  toxicity  of  bile,  since  it,  when  once  decolorized,  becomes  much  less 
toxic.  Toxicity  of  bilirubin. 

WE  must  now  deal  with  the  problem  of  the  origin  of  the 
toxic  substances  which  urine  contains.  Whence  does  urine 
obtain  its  toxicit}'  ?  We  have  established  the  fact  that  the 
orgnnism  forms  toxic  products,  and  that  the  kidney  eliminates 
them.  It  is  now  for  us  to  show  whether,  on  the  side  of  the  kid- 
ney, there  is  anything  toxic  in  the  blood  and  in  the  tissues. 
A  priori,  it  is  physiologically  inadmissible  that  normal  blood 
can  be  toxic.  If  it  was,  the  animal  could  not  live.  We  know 
that  urine  may  be  toxic — such  as  when  found  outside  of  the 
organism — in  a  reservoir  from  which  it  cannot  be  re-absorbed  in 
the  natural  state;  but  blood  itself  cannot  be,  circulating,  as  it 
does,  in  vessels  which  are  not  opposed  to  its  diffusion  into  the- 
tissues.  If  blood  is  not  toxic,  it  is  because  normal  urine  is,  and 

(69) 


70  LECTURES   ON   AUTO-INTOXTCATION. 

is  incessantly  removing  toxicity  from  it.  The  blood  is  con- 
tinually being  traversed  by  a  current  of  toxic  material.  It  is 
true  that  the  poison  is  never  found  in  it  but  in  harmless  quan- 
tities. There  is  less  toxic  matter  in  the  blood  than  in  the 
organs.  The  anatomical  elements  form  substances  which,  if 
retained,  would  fetter  their  life,  but  these  substances  leave  them, 
little  by  little,  in  order  to  penetrate  into  the  blood.  The  quan- 
tity of  toxic  matter  eliminated  by  the  kidneys  in  twenty-four 
hours  is,  without  doubt,  one-half  of  what  is  necessary  to  kill  the 
whole  of  the  body,  and  the  blood  has  really  received  that  quan- 
tity in  twenty-four  hours ;  but  the  elimination  is  incessant,  and 
at  every  instant  of  the  day  the  blood  never  contains  at  one  time 
more  than  an  infinitely  small  fraction  of  poison. 

The  estimation  of  those  fractions  ma}'  be  made  for  units  of 
time ;  that  is  to  say,  for  a  complete  revolution  of  the  blood,  say 
about  forty-seven  seconds,  taking  into  account  certain  slower  revo- 
lutions which  take  place  in  certain  departments  of  the  vascular 
system.  A  man  of  65  kilogrammes  expels  in  twenty-four  hours 
1350  cubic  centimetres  of  urine,  which  kill  1  kilogramme  of  rabbit 
with  a  dosage  of  45  cubic  centimetres.  This  man  eliminates, 
therefore,  in  twenty-four  hours,  by  his  urine,  sufficient  to  kill 
~  =  30  kilogrammes  of  living  matter.  The  whole  quantity  of 
blood  of  this  man  is  jg  —  5  kilogrammes.  The  five  kilogrammes 
of  blood  of  this  man  are  thus  traversed  in  twenty-four  hours  by 
a  quantity  of  poison  capable  of  killing  30  kilogrammes. 

The  number  of  complete  circulatory  revolutions  is  1850  in 
twenty-four  hours.  In  each  complete  revolution  the  kidneys 
remove  from  5  kilogrammes  of  blood  a  quantity  of  poison  capable 
of  killing  J^,  and  from  1  kilogramme  of  blood  185^°X5=  0.003243 
kilogramme,  or  3.243  grammes.  If,  during  a  complete  revolu- 
tion, each  kilogramme  of  blood  discharges  a  quantity  of  poison 
capable  of  destroying  3.243  grammes  of  animal  substance,  in 
the  same  time  this  mass  of  poison  will  be  furnished  to  each 
kilogramme  of  blood  by  the  organism,  the  in-going  being  equal  to 
the  out-going.  It  follows  from  this  that  the  blood  ought  to  con- 
tain constantly ,  at  the  least, this  quantity  of  poison.  It  ought  even 
to  contain  more,  for  the  blood  is,  during  each  cardiac  revolution, 
only  deprived  of  a  fraction  of  its  quantity  of  poison  by  the  renal 


RAPIDITY   OF    ELIMINATION.  71 

emunctory.  It  is  probable  that  there  is  in  the  blood  more  toxic 
material  than  this  minimum  portion  which  penetrates  there,  and 
which  leaves  it  during  the  forty-seven  seconds  of  a  complete 
revolution,  and  that  there  is  a  reserve  of  toxic  material  circulating 
with  the  blood.  Analogy  helps  to  show  us  that  it  is  thus  as  it 
ought  to  be,  and  it  will  enable  us  to  appreciate  hypothetically 
the  importance  of  this  reserve. 

A  man  of  65  kilogrammes  eliminates  in  twenty-four  hours, 
by  1350  cubic  centimetres  of  urine,  1300  grammes  of  water  and 
24  grammes  of  urea.  In  a  complete  circulatory  revolution  he 
eliminates  1850  times  less  of  each  substance, — that  is,  O.T  gramme 
of  water  and  0.01297  gramme  of  urea.  These  quantities  of 
water  and  of  urea  are  given  up  by  5  kilogrammes  of  blood. 
One  kilogramme  of  blood  gives,  therefore,  during  one  total  revo- 
lution, five  times  less,  or  0.14  gramme  of  water  and  0.002592 
gramme  of  urea.  But  this  kilogramme  of  blood  only  gives  up 
these  quantities  of  material  from  its  liquid  part, — from  its 
plasma, — which  only  constitutes  one-half  of  the  mass  of  blood  ; 
and  the  500  grammes  of  plasma  in  1  kilogramme  of  blood  con- 
tain only  450  grammes  of  water  and  0.16  gramme  of  urea.  The 
calculation  made,  the  blood  loses,  during  a  complete  revolution, 
SST?  Pai't  °f  water  from  its  plasma  and  ^  part  of  urea  from 
its  plasma,  which  proves,  as  I  established  in  1872,  that  urea  is 
eliminated  by  the  kidney  fift}r-two  times  quicker  than  the  water 
(£=M). 

If  the  rapidity  of  the  elimination  of  the  blood-poison  was 
equal  to  that  of  urea,  1  kilogramme  of  blood  would  contain 
sixty-two  times  the  quantity  of  poison  which  this  kilogramme 
of  blood  eliminates  in  a  complete  revolution  ;  and  as  this  quan- 
tity eliminated  is  capable  of  killing  3.243  grammes  of  living 
matter,  1  kilogramme  of  blood  ought  to  contain  sufficient  poison 
to  kill  3.243  X  62  =  201  grammes  of  living  matter,  which  repre- 
sents a  minimum  of  toxicity. 

If,  on  the  contrary,  the  rapidity  of  the  elimination  of  the 
poison  was  equal  to  that  of  the  water,  the  quantity  of  toxic 
matter  inclosed  in  1  kilogramme  of  blood  ought  to  be  3214 
times  the  quantity  eliminated  by  this  kilogramme  of  blood 
during  a  complete  revolution.  One  kilogramme  of  blood  would, 


72  LECTURES  ON   AUTO-INTOXICATION. 

therefore,  be  capable  of  killing  3.243X3214=10,423  grammes 
of  living  tissue.  This  result  is  not  preposterous  ;  this  maxi- 
mum of  toxicity  would  not  be  incompatible  with  life.  With 
such  a  toxicity  of  its  blood  the  animal  would  poison  itself,  if  1 
kilogramme  of  blood  was  distributed  'to  10  kilogrammes  of 
its  body ;  but,  in  reality,  1  kilogramme  of  blood  is  distributed 
to  13  kilogrammes  of  the  organism.  It  is,  moreover,  extremely 
probable  that  the  real  toxicity  of  the  blood  is  less,  and  that  it 
is  comprised  between  these  two  extremes. 

These  hypothetical  calculations  only  show  us  the  extreme 
limits  of  the  possible  toxicity  of  the  blood.  We  can,  fortu- 
nately, approach  the  question  from  the  experimental  side.  The 
injection  of  the  blood  of  an  animal  into  the  veins  of  another 
animal  can  produce  death  without  this  death  being  attributable 
to  embolism  and  without  the  augmentation  of  the  mass  of 
blood  being  incriminated.  The  injection  of  25  cubic  centi- 
metres of  blood  per  kilogramme  of  animal  invariably  causes 
death.  What  proves  that  death  in  such  is  the  result  of  an 
intoxication  is  that  the  fatal  dose  varies  according  to  the  part 
of  the  vascular  apparatus  from  which  this  blood  has  been  with- 
drawn. If,  instead  of  drawing  it  from  the  general  venous 
system,  we  draw  it  from  the  portal  vein,  14  cubic  centimetres 
are  sufficient  to  cause  death,  instead  of  25, — this  blood  being 
charged  with  putrid  and  biliary  poisons  taken  from  the  intestine, 
and  not  having  them  as  yet  removed  from  it  by  the  liver.  But 
a  kilogramme  of  animal  contains  ^=77  grammes  of  blood. 
After  the  injection  of  25  grammes  of  blood,  this  kilogramme 
would  contain  102  grammes,  and  then  the  animal  dies.  We  ma}' 
therefore  say  that  102  grammes  of  blood  are  sufficient  to  kill  1 
kilogramme  of  animal.  In  other  words,  1  kilogramme  of  venous 
blood  retains,  in  the  normal  state,  sufficient  poison  to  kill  9804 
grammes  of  living  matter. 

These  conclusions  would  be  strictly  exact  if  the  blood 
injected  came  from  an  animal  of  the  same  species  as  that  into 
which  we  make  the  injection.  But,  in  my  experiments,  it  is  the 
blood  of  the  dog  which  has  been  injected  into  the  rabbit.  I 
have  reasons  for  believing  that  the  blood  is  more  toxic  for  an 
animal  of  another  species  than  for  an  animal  of  the  same  species. 


EFFECTS  OF  INJECTION  OF  BLOOD.  73 

In  experimental  studies  bearing  upon  transfusion,  we  have 
properly  said  that  the  blood  of  one  species  is  poisonous  to 
another,  but  we  have" not  made  the  estimation  of  the  degree  of 
this  toxicity,  and  we  have  always  gone  away  from  this  point 
with  a  false  view  that  the  blood  of  an  animal  is  not  toxic  for  an 
animal  of  the  same  species.  Whilst  the  blood  of  the  dog  kills 
a  rabbit  at  the  dose  of  25  cubic  centimetres  per  kilogramme, 
I  have  known  the  blood  of  the  dog  injected  into  another  dog  to 
the  extent  of  30  cubic  centimetres  only  produce  a  fleeting- 
indisposition,  whilst  in  the  rabbit,  in  order  to  cause  death,  it 
is  necessary  to  inject  126  cubic  centimetres  of  blood  of  rabbit. 
This  amount  is  considerable.  It  is  true  that  it  was  a  question 
6f  the  injection  of  arterial  blood.  Death  supervened  by  con- 
vulsions, with  moderate  pupillary  contraction.  The  urine  con- 
tained only  traces  of  albumen, — none  of  blood,  none  of  haemo- 
globin. There  were  no  haemorrhages  into  any  organ,  except 
from  embolic  foci, — numerous  enough,  but  very  small, — of 
pulmonary  apoplexy,  to  which  death  could  not  be  attributed, 
the  respiratory  rhythm  not  having  been  modified  before  the 
final  convulsion,  which  was  very  short.  In  this  experiment  the 
animal  died  when  each  kilogramme  of  its  body  was  irrigated  by 
77  +  126  =  203  grammes  of  blood.  From  this  we  infer  by  cal- 
culation that  1  kilogramme  of  rabbits'  blood  is  capable  of  killing 
4926  grammes  of  rabbit, — in  round  numbers,  5  kilogrammes. 
And  we  still  further  draw  the  inference,  if  you  wish  to  refer  to 
calculations  just  recently  made,  that  l>y  the  kidneys  the  poisons 
of  the  blood  should  be  eliminated  twice  more  quickly  than  the 
water,  but  twenty-six  times  slower  than  urea.  This  remark  is 
not  without  some  interest.  It  shows  that  if  the  kidney  cannot 
be  got  to  eliminate  urea,  it  may  succeed  in  expelling  blood- 
poisons,  and  that,  in  the  case  of  auto-intoxication,  the  witli- 
drawal  of  large  quantities  of  serum,  or  merely  of  water,  might 
not  be  without  some  utility.  One  last  conclusion  to  draw  from 
the  experiment  is  that,  in  order  that  death  may  be  produced  by 
auto-intoxication,  it  is  sufficient  that  the  amount  of  the  poisons 
of  the  blood  should  become  two  and  one-half  times  greater  than 
the  normal  quantity. 

I  give  you  the  different  steps  by  which  I  have  entered  into 


74  LECTURES  ON   AUTO-INTOXICATION. 

this  study  of  the  toxicity  of  blood, — the  l^pothesis,  calculation, 
and  experiment.  I  have  no  difficulty  in  recognizing  that  more 
recent  experiments  have  obliged  me  to  admit  that  blood  has  a 
toxicity  still  less  than  that  which  seems  should  be  inferred  from 
the  preceding  experiment.  In  blood,  the  plasma  alone  may  be 
toxic.  The  living  cells  retain  within  themselves  the  inert  or 
hurtful  substances  of  which  they  are  composed.  In  order  that 
these  poisons  may  act,  it  is  absolutely  necessary  that  they  should 
be  in  solution  ;  it  is  necessary  that  they  should  dialyze  from  the 
blood  into  the  tissues ;  it  is  necessary  that  they  should  be  in  the 
liquid  part, — non-living, — in  the  plasma.  There  has,  therefore, 
been  good  cause  for  experimenting  upon  the  toxicity  of  the 
blood-serum.  I  have  extracted  from  ten  rabbits,  by  arterial 
bleeding,  600  grammes  of  blood.  The  clot,  after  having  been  in 
an  ice-box  for  twenty-four  hours,  has  furnished  to  me  260 
grammes  of  a  limpid  serum,  scarcely  tinged.  This  serum  has 
been  filtered  and  then  injected  into  the  veins  of  a  rabbit.  The 
animal  died,  after  having  received  125  cubic  centimetres  of 
serum  per  kilogramme.  Death  was  preceded  by  a  distinct,  but 
not  punctiform,  contraction  of  the  pupil, — by  exorbitism,  by 
dilatation  of  the  superficial  veins,  and,  in  the  last  moments,  by 
the  loss  of  ocular  reflexes,  b}-  convulsions,  and  by  a  frothy,  san- 
guineous running  from  the  nostrils.  The  lungs,  voluminous  but 
pale,  were  dotted  with  patches  of  pulmonary  apoplexy.  There 
were  no  haemorrhages  at  any  other  point  in  the  body.  •  The  urine 
contained  neither  blood  nor  albumen.  The  heart  continued  to 
beat  for  a  long  time  after  death. 

The  serum  constitutes  about  one-half  of  the  mass  of  blood. 
I  have  injected,  in  this  experiment,  the  poison  dissolved  from 
250  grammes  of  blood.  The  animal  had  already  in  its  vessels, 
before  the  injection,  77  grammes  of  blood.  When  it  died,  its 
tissues  had  at  their  disposal,  per  kilogramme  of  its  weight,  the 
poison  of  327  grammes  of  blood  ;  from  this  I  am  obliged  to 
conclude  that  1  kilogramme  of  blood  is  capable  of  killing  about 
3  kilogrammes  of  animal. 

Was  death,  in  this  experiment,  due  to  toxicity  of  the  blood 
alone?  I  would  not  dare* to  say  so.  I  am  obliged  to  take  some 
cognizance  of  the  apoplectic  patch  in  the  lung  and  of  the  san- 


IS  BLOOD   MORE   TOXIC   THAN   WATER?  75 

guinolent  oozing  from  the  nostrils,  which  suggest  the  idea  of 
plethoric  haemorrhages,  and  which  raise  the  question  whether 
the  enormous  increase  in  the  mass  of  blood  has  not  been  the 
cause  of  death.  Remember,  however,  that  the  animal  died, 
after  having  received  into  its  veins  125  cubic  centimetres  of 
serum,  like  the  animal  in  the  preceding  experiment,  after 
having  received  126  cubic  centimetres  of  defibrinated  blood.  Re- 
member, too,  that  distilled  water  causes  death  when  we  intro- 
duce into  the  vessels  more  than  122  cubic  centimetres  of  it. 
From  this  comparison  you  will  be  able  to  conclude  that  blood  is 
less  toxic  than  pure  water.  It  is  ou\y  apparently  so,  and,  at  the 
same  time,  a  misuse  of  language.  Water  is  not  toxic,  properly 
speaking,  and  a  liquid  which  kills  in  a  larger  dose  than  water 
may  be  toxic.  Water  does  not  kill  by  its  chemical  composition, 
by  toxicity ;  nor  does  it  kill  ain*  more  by  its  mechanical  action, 
— by  plethora;  it  kills  by  its  phj-sical  action,  by  swelling  out 
the  globules  and  dissolving  out  the  haemoglobin.  If  you  wish, 
to  know  to  what  point  it  is  requisite  to  increase  the  mass  of 
blood  in  order  that  death  may  follow,  or  what  is  the  limit  at  which 
plethora  becomes  fatal,  it  is  necessaiy,  as  I  have  done,  to  inject 
into  the  veins  water,  to  which  a  salt  very  slightly  toxic  has  been 
.•uldrd,  and  in  such  proportion  that  in  this  solution  the  globules 
of  the  blood  are  not  deformed, — a  solution  of  sea-salt,  7  parts  in 
1000, — an  artificial  serum.  Yet,  with  such  a  liquid,  death  comes 
in  the  rabbit  only  when  we  have  injected  for  each  kilogramme  396 
cubic  centimetres  of  the  solution,  or  when  we  have  multiplied  the 
mass  of  the  blood  six  times.  In  such  it  is  really  with  plethora 
that  we  have  to  deal ;  death  is  the  result  of  a  mechanical  effect, 
for  during  life  the  veins  are  seen  to  be  extremely  distended, 
injection  becomes  difficult  and  laborious,  and  the  piston  of  the 
syringe  is  constantly  driven  back  by  the  excess  of  the  intra- 
venous tension.  All  the  liquid  injected  remains  in  the  circulatory 
apparatus,  for  the  urinary  secretion  is  not  increased  ;  we  do  not 
find  liquid  either  in  the  stomach,  intestines,  or  serous  cavities, 
and  there  is  no  oedema  in  any  part,  but  we  detect  a  focus  of 
pulmonary  apoplexy.  There  has  not  been  any  physical  action, 
for  the  blood-globules  are  neither  deformed  nor  decolorized  ; 
there  has  not  been  any  chemical  or  toxic  action,  for  we  have 


76  LECTURES   ON   AUTO-INTOXICATION. 

only  injected  2.772  grammes  of  sodium  chloride,  and  to  kill  a 
kilogramme  of  rabbit  we  require  5.31  grammes  of  this  salt. 
If  in  order  to  kill  by  plethora  we  must  increase  the  mass  of 
blood  six  times, — I  have  not  even  tripled  it  in  my  injections  of 
serum  or  of  blood, — I  add  that  in  these  experiments  death  can- 
not be  explained  by  a  physical  action,  as  when  there  is  question 
of  distilled  water.  I  have  introduced  into  the  veins  a  liquid 
which  is  the  natural  medium  of  the  globules,  in  which  they 
neither  become  swollen  nor  retracted.  I  come  therefore  to  my 
first  conclusion, — death  is  apparently  only  explained  by  intoxi- 
cation ;  but,  notwithstanding,  I  maintain  a  reserve,  for  it  is  not 
poisoning  which  could  have  provoked  pulmonary  apoplexy ; 
something  must  have  been  added  to  the  intoxication. 

To  avoid  this  something,  we  would  require  to  inject  the 
poison  of  the  serum  in  a  state  of  greater  concentration, — the 
removal  of  the  water,  the  removal,  too,  of  albuminoids,  which,  I 
suppose,  cannot  be  the  toxic  substances  ;  at  least,  when  we  inject 
blood  from  one  species  into  an  animal  of  the  same  species. 
That  is  what  I  have  done ;  I  have  coagulated  the  albumen  and 
concentrated  by  freezing  the  liquid  got  by  washing  the  coagu- 
lum.  In  order  to  produce  death,  I  have  been  obliged  to  inject 
the  extract  from  more  than  400  grammes  of  serum  representing 
800  grammes  of  blood  ;  yet  it  was  simply  the  extract  from  the 
serum  of  horse  injected  into  the  rabbit.  In  this  experiment, 
1000  of  blood  would  kill  1250  of  living  matter.  Calculation  has 
forced  us  to  admit  that  a  kilogramme  of  blood  would  be  capable 
of  killing  at  the  least  201  grammes,  and  at  the  maximum  10,423 
grammes  of  living  matter — experimentation  has  narrowed  these 
extreme  limits.  It  shows  us  that  a  kilogramme  of  blood  could 
destroy  at  the  least  1250  grammes,  and  at  the  greatest  3000 
grammes  of  living  matter.  The  true  index,  as  yet  undetermined,  is 
between  these  two  extremes.  Besides  the  plasma,  blood  contains 
globules.  Do  these  globules  increase  the  toxicity  of  the  blood  ? 
Experimental^-,  no  ;  yet  these  globules  contain  toxic  materials, 
and  even  in  large  quantity;  but  they  are  materials  belonging  to 
the  constitution  of  the  globules,  and  these  are  living.  Blood  is 
only  a  tissue  of  mobile  cells,  which  haAre,  like  every  cell,  a  frame- 
work. What  enters  into  the  composition  of  this  frame-work  is 


CELLS  IN   THEIR  DESTRUCTION   LIBERATE   POISONS.  77 

inoffensive  for  the  cell  so  long  as  it  is  living ;  but  each  cell  con- 
tains potass,  which  it  keeps  combined  with  other  substances, 
mineral  or  organic.  This  potass  cannot  injure  living  cells  except 
when  liberated  by  the  destruction  of  other  cells ;  in  these  con- 
ditions potass  passes  into  the  liquids  and  its  toxicity  may  then 
be  shown.  If  we  destroy  the  globules  by  boiling  or  by  charring 
and  inject  the  aqueous  solution  of  this  into  the  blood  of  an 
animal,  we  bring  about  convulsions  and  death. 

Alcohol  removes  water  from  the  globules,  extractive  matters, 
fat,  cholesterin,  and  the  salts  of  potass.  With  the  alcoholic 
extracts  of  blood  we  induce  muscular  weakness,  convulsions, 
,  and  very  rapidly  salivation,  as  I  pointed  out  apropos  of  a 
toxic  substance  in  urine.  It  is  from  the  blood  that  the  kidney 
gets  this  substance,  which  causes  salivation.  With  the  alco- 
holic extract  of  blood,  narcosis  is  observed  only  under  abnormal 
circumstances.  I  have  seen  it  produced  in  one  case  with  the 
blood  of  a  uraemic  patient  who  was  not  eliminating  its  toxic 
substances,  but  with  normal  blood  we  do  not  induce  narcosis. 
Into  the  alcoholic  extracts  of  blood  there  pass  nitrogenous 
bodies,  both  basic  and  neutral ;  I  cannot  say  to  which  of  them 
the  physiological  phenomena  of  which  I  speak  are  due.  I  con- 
sider that  the  living  globules  are  harmless,  but  that  they  furnish 
toxic  matter  when  they  are  destroyed.  I  can  only  incriminate 
the  potass  liberated  by  this  destruction.  I  cannot  always 
accuse  the  alkaloids  found,  in  normal  blood,  by  Gautier  and 
myself,  for  they  are  found  in  a  still  smaller  quantity  than  that 
which  urines  contain,  and  we  have  seen  that  they  represent  only 
a  minimum  part  of  the  toxicity  of  urine. 

En  resume,  blood  contains,  as  we  know,  a  reserve  quantity  of 
poison;  a  small  quantity  of  this  poison  is  incessantly  eliminated 
by  the  kidneys ;  it  receives  from  the  tissues  an  equal  quantity 
of  it ;  it  contains,  therefore,  in  the  normal  state,  alwa3*s  a  cer- 
tain quantity.  If  elimination  is  prevented  and  the  supply  of  it 
continues,  accumulation  of  toxic  material  produces  intoxication. 
We  know  what  the  quantity  of  toxic  matter  is  that  is  introduced 
into  the  blood  and  eliminated  by  the  kidney  in  a  circulatory 
revolution,  and  we  also  know  what  quantity  of  living  matter 
might  be  killed  by  this  amount  of  toxic  material ;  we  can,  then, 


78  LECTURES   ON    AUTO-INTOXICATION. 

fix  the  time  necessary  for  1  kilogramme  of  blood  to  kill  1  kilo- 
gramme of  animal.  This  period  is  two  days  and  four  hours ; 
that  is  a  theoretical  average.  In  reality  the  time  necessary  is 
longer,  because  in  uraemia  there  are  produced  functional  derange- 
ments of  the  intestinal  tube  which  prevent  it  absorbing  the 
poisons  which  it  contains,  were  it  only  the  potass  of  alimentary 
origin ;  moreover,  the  formation  of  the  poisons  of  disassimila- 
tion  is  prevented  by  intoxication  itself;  vomiting,  chill.  The 
poisons  only  act  when  dissolved  in  the  plasma ;  the  globules  are 
not  toxic  whilst  they  remain  alive.  The  materials  constituting 
these  anatomical  elements  are  retained  therein  by  the  force  of 
tension  which  resides  in  every  living  cell ;  but  in  case  of  death  or 
rapid  disintegration  of  the  cell,  freedom  is  given  to  all  the  sub- 
stances which  were  part  of  its  constitution, — potass,  creatin, 
leucin,  and  other  nitrogenous  substances.  The  proteid  matters 
would  themselves  be  incriminated  if  it  is  true  that  they  can,  by 
undergoing  certain  modifications,  pass  into  the  condition  of  soluble 
ferments ;  the  experiments  of  Alex.  Schmidt  would  tend  to  make 
this  a  supposition.  In  every  case,  in  spite  of  the  work  of  the 
school  of  Dorpat,  I  do  not  believe  that  the  intoxication  pro- 
duced by  blood  can  be  attributed  to  dissolved  haemoglobin. 
The  result  of  the  sudden  or  rapid  destruction  of  blood-corpuscles 
is  the  production  of  such  phenomena  as  muscular  debility,  sali- 
vation, convulsions,  and  death,  but  never  narcosis,  unless  when 
we  operate  with  the  blood  of  a  person  who  is  ursemic  or  is  suf- 
fering from  choleraic  anuria.  Of  those  effects,  some  are  due  to 
the  mineral  constituents ;  from  the  potass,  notably  the  convulsive 
phenomena  arise ;  of  the  organic  substances  there  is  one  which 
is  present  in  the  alcoholic  extract  of  blood  and  urine,  liver  and 
muscle,  and  to  which  salivation  is  attributed. 

After  having  studied  the  toxicity  of  the  blood,  it  would  be 
desirable  to  get  to  know  the  toxicity  of  the  tissues.  But  this  is 
a  still  more  delicate  research ;  we  cannot  inject  them  as  they  are 
into  animals  ;  we  can  only  inject  their  extracts,  and  these  ex- 
tracts, these  products  of  the  disintegration  of  tissues,  are  toxic. 
The  toxicity  of  the  extract  of  flesh  has  been  known  for  a  long 
time.  This  may  be  of  some  utility  from  an  alimentary  point  of 
view  ;  to  a  certainty  it  is  toxic.  Jf  it  does  not  poison,  that  is 


LIFE   WITHOUT   FREE   OXYGEN.  .  79 

because  it  has  been  introduced  only  in  small  quantity  into  the 
organism,  and  that  it  is  being  constantly  eliminated  ;  besides,  in 
every  aliment  there  are  toxic  substances,  and  every  aliment 
would  become  a  poison  if  renal  elimination  was  not  the  safe- 
guard of  the  body.  It  is  said  that  what  is  toxic  in  the  extract 
of  meat  besides  the  mineral  salts,  potass,  are  organic  substances, 
such  as  creatinin,  which  in  meat  is  in  the  form  of  creatin.  The 
stimulating  effects  after  muscular  depression  are  attributable 
to  it. 

With  the  aqueous  extract  of  muscle,  which  contains  mineral 
and  organic  substances,  we  produce  neither  salivation  nor  nar- 
•cosis,  but  convulsions,  and,  exceptionally,  contraction  of  the 
pupil.  In  these  phenomena  of  intoxication  there  is  no  place  for 
the  action  of  alkaloids ;  the  alcoholic  extract  of  muscle  causes 
the  salivation.  An  alcoholic  extract  of  liver  causes  an  excessive 
salivation;  the  extract  from  117  grammes  of  liver  determines 
death  in  the  rabbit.  When  we  know  the  toxicity  of  an  extract, 
if  we  suppress  the  potass  which  it  contains,  we  deprive  it  of  its 
power  of  producing  convulsions.  For  this  purpose  it  is  suffi- 
cient to  precipitate  it  in  the  state  of  tartrate  of  potass.  After 
this  operation  the  extract  of  216  grammes  of  muscle,  which 
caused  convulsions  and  death,  produces  no  accident  whatever. 
Besides  potass,  there  exist  in  the  extracts  of  the  tissues  such 
bodies  as  tyrosin,  leucin,  butyric  and  acetic  acids;  they  play 
their  part  in  those  phenomena  of  intoxication,  during  life,  com- 
parable to  those  which  supervene  after  the  absorption  of  the 
poisons  of  putrefaction. 

Here  is  a  remark  of  Gautier :  "  By  the  side  of  aerobic  life 
there  is  anaerobic  life,  thanks  to  which  the  cell  is  able  to  live 
for  some  time  without  oxygen.  The  anatomical  elements  are 
still  engaged  in  the  phenomena  of  oxidation,  but  at  this  time 
they  are  taking  oxygen  into  the  tissue  itself.  If  we  weigh  the 
respired  oxygen,  that  mixed  with  the  fluids  drunk  and  in  combi- 
nation with  the  food,  and  on  the  other  side  the  oxygen  fixed  in 
the  carbonic  acid  exhaled  by  the  lungs, the  skin, contained  in  the 
dejections  and  combined  in  the  excreta,  we  find  absolute  equality 
on  both  sides.  But  the  free  oxygen  has  not  been  sufficient;  the 
respired  oxygen  does  not  explain  the  surplus  of  water  and  cur- 


80  .  LECTURES   ON   AUTO-INTOXICATION. 

bonic  acid ;  the  oxidations,  therefore,  have  been  made  with  the 
oxygen  of  the  combinations ;  one-third  of  life  is  supported  by 
oxidation  without  free  oxygen."  Nutrition  is  thus,  on  one  side 
at  least,  comparable  to  fermentation  when  air  is  excluded. 

Let  us  return  to  the  liver  and  to  its  particular  emunctory 
function.  Bile  plays,  without  doubt,  a  part  in  digestion,  but  it 
is  a  constituent  of  the  excreta,  and  it  undergoes,  in  part,  ab- 
sorption. Does  the  part  absorbed  produce  intoxication  ?  Schiff 
has  told  us  that  we  can  find  bile  in  the  blood  just  come  from 
the  intestine,  but  not  in  the  general  circulation.  He  has  ad- 
mitted that  the  bile  is  seized  again  by  the  liver,  then  secreted 
anew,  and  again  retaken  without  cessation.  If  this  perpetual 
circle  is  true,  the  liver  would,  therefore,  act  as  a  protector  to 
the  general  circulation,  as  regards  bile  and  other  poisons.  That 
is  possible,  but  not  emphatically  demonstrated.  In  every  case 
the  contrary  is  true  in  pathological  conditions ;  bile  may  im- 
pregnate the  blood  and  tissues.  Even  in  the  normal  state,  in  the 
dog,  bile  passes  into  the  whole  of  the  circulation ;  in  this  animal 
jaundice  is  physiological. 

To  return  to  man,  may  bile  itself  cause  in  him  intoxication  ? 
For  a  long  time  we  have  suspected  the  toxicity  of  bile.  Deidier, 
in  the  last  century,  made  intra-venous  injections  of  bile  from 
those  who  died  of  the  plague.  In  our  own  century,  at  different 
times,  there  have  been  undertaken  experiments  to  clear  up  this 
question.  Bouisson  concluded  that  filtered  bile  is  inoffensive ; 
that,  unfiltered,  it  kills.  It  can  bring  about,  like  all  viscid 
liquids, — like  pure  glycerin, — pulmonary  embolisms.  Von 
Dusch,  Frerichs,  and  Bamberger  have  injected  large  doses  of  it, 
and  have  only  rarely  induced  death.  Vulpian  has  injected  up  to 
250  grammes  of  it  into  a  dog  during  several  days, — 96  grammes 
in  one  day  alone.  He  has  omitted  to  mention  the  weight  of  the 
dog.  Supposing  it  to  weigh  10  kilogrammes,  the  toxicity  of  the 
bile  would  be  9  cubic  centimetres  per  kilogramme  of  the  animal, 
— that  is  to  say,  five  or  six  times  stronger  than  that  of  urine. 
That  is  little,  when  we  think  of  the  fatal  consequences  which 
are  attributed  to  bile.  I  have  established  that  the  bile  of 
oxen,  mixed  in  twice  its  volume  of  water  and  injected  into 
the  veins  of  a  rabbit,  produces  death  in  the  dose  of  4  to  6  cubic 


TOXICITY   OF   BILE.  81 

centimetres  of  pure  bile  for  each  kilogramme  of  animal.  I 
have  recognized,  besides,  that  bile  decolorized  by  carbon  loses 
two-thirds  of  its  toxicity. 

Of  the  toxicity  of  bile,  numerous  explanations  have  been 
offered.  The  biliary  salts  have  been  declared  toxic  in  almost 
infinitesimal  quantities ;  they  have  been  found  in  such  small 
quantity  in  the  blood  of  those  who  have  died  from  severe  jaun- 
dice and  from  poisoning  by  phosphorus.  Injections  of  tauro- 
cholate  and  glycocholate  of  soda,  made  by  von  Dusch,  Huppert, 
and  Kuhne,  have  produced  scarcely  any  effect  whatever.  And 
yet  the  results  obtained  by  Leyden  upon  the  dog  and  frog  have 
'little  in  agreement  with  each  other.  Concurrently  with  M. 
Tapret,  I  have  determined  that  the  biliary  salts  in  an  aqueous 
solution  of  2  per  cent,  kill  1  kilogramme  of  rabbit ;  the  cholate 
of  soda,  in  the  dose  of  54  centigrammes ;  and  choleate  of  soda, 
in  the  dose  of  46  centigrammes. 

We  might  incriminate  cholesterin,  but  we  have  only  been 
able  to  induce  cholesteraemia  experimentally,  by  processes  too 
defective  to  enable  us  to  draw  from  them  any  conclusion.  The 
absurd  quantities  of  cholesterin  which  have  been  introduced 
into  the  blood  have  only  been  done  through  the  medium  of  soap 
and  water,  or  of  potass,  which  would  kill  of  themselves.  At 
any  rate,  amongst  old  people,  the  atheromatous  abscesses  which 
we  find  widely  open  in  the  aorta  contain  sometimes  several 
grammes  of  cholesterin  without  there  being  any  poisoning  from 
them.  The  coloring  substances  ought  to  be  suspected  by  us  as 
toxic  agents,  since  bile,  once  decolorized,  is  much  less  toxic. 
Equally  with  M.  Tapret,  I  have  shown  that  bilirubin  kills  in 
the  dose  of  5  centigrammes  per  kilogramme. 

As  for  the  biliary  salts,  they  do  not  kill  by  direct  intoxica- 
tion alone.  We  can  see  under  the  microscope  the  harm  which 
they  do.  They  dissolve  and  break  up  the  blood-globules,  and 
also  other  cells, — striated  muscular  fibres,  and  the  cells  of  the 
liver.  They  therefore  cause  anatomical  lesions,  and  intoxication 
arises  from  the  setting  free  of  toxic  substances  which  enter  into 
the  composition  of  the  cellular  elements.  This  intoxication 
develops  but  slowly. 

People  intoxicated  by  bile  are,  therefore,  in  the  condition  of 


82  LECTURES   ON    AUTO-INTOXICATION. 

animals  into  whom  we  have  injected  aqueous  or  alcoholic  extracts 
of  the  tissues.  Amongst  patients,  so  long  as  there  is  functional 
activity  of  the  kidney,  all  goes  on  well ;  but  if  not,  then  they 
die  intoxicated  by  the  potass  and  by  other  products  of  cellular 
destruction.  But  it  is  not  a  primary  intoxication ;  it  is 
secondary,  and  is  caused  by  the  mineral  or  organic  products, 
and  from  the  breaking  up  of  the  anatomical  elements. 

Amongst  jaundiced  people,  we  indeed  observe  a  rapid  dimi- 
nution of  the  weight  of  the  body.  In  acute  yellow  atrophy  of 
the  liver,  it  seems  that  the  muscles  diminish  in  size.  Besides, 
if  the  kidney  functionates  well  in  jaundiced  people,  their  urine 
is  very  toxic,  but  not  in  the  same  manner  as  normal  urine.  This 
does  not  determine  convulsions  ;  jaundiced  urine  is  convulsive, 
and  not  narcotic.  In  small  doses,  even  absolutely  decolorized, 
it  remains  toxic  ;  but  it  does  not  owe  this  property  to  the  con- 
vulsive material  of  normal  urine,  since  this  remains  fixed  in  the 
carbon.  The  convulsive  property  comes  to  it  probably  from  the 
potass,  for  bile  produces  nothing  similar  to  it.  Thus,  jaundiced 
urines  owe  their  toxicity  chiefly  to  the  waste  products  of  cellular 
disintegration,  and  especially  to  the  mineral  products.  We  are 
now  beginning  to  foresee  what  intoxication  may  be  in  the 
economy. 


LECTURE  VIII. 

ORIGIN  OF  THE  Toxic  SUBSTANCES  OF  URINE — TOXICITT  OF  THE 

FLUIDS  AND  OF  THE  CONTENTS  OF  THE   INTESTINE  (BlLE  AND   THE 

PRODUCTS  OF  PUTREFACTION). 

Toxicity  of  the  fluids.     It  is  due  to  the  disassimilation  or  destruction  of  cells. 

Products  of  disassimilation  turned  into  the  intestine  by  the  liver.     Toxic 

power  of  bile  compared  with  that  of  urine.  Dangers  of  absorption  or  reten- 
tion of  bile.  How  the  organism  protects  itself  against  the  toxicity  of  bile. 
Precipitation  of  a  part  of  the  biliary  elements  in  the  intestine  and  metamor- 
phoses having  for  their  object  the  insolubility  of  other  elements  ;  toxicity  of 
jaundiced  urines  ;  diminution  of  the  toxic  power  of  jaundiced  urine  brought 

'  about  by  decolorizing. Putrefaction  in  the  intestine  caused  by  microbes 

which  are  found  normally  therein.    Role  of  the  hydrochloric  acid  of  the 

gastric  juice  which  neutralizes  the  activity  of  these  microbes. Are  putrid 

substances  toxic?  Opinion  of  Haller.  Experiments  of  Gaspard,  Pamnn, 
Bergmann,  Billroth.  Koch's  argument. 

IF  animal  juices  are  scarcely  toxic,  although  they  contain 
more  poison  than  the  quantity  which  they  give  up  to  the  emunc- 
tories,  the  cells  enclose  poisonous  substances  which  they  retain 
because  these  substances  are  part  of  their  constitution,  and  which, 
freed  by  the  death  of  the  cells,  cause  the  fluids  to  become  toxic. 

These  toxic  matters  are  substances  organized  and  mineral. 
PotMss  occupies  the  first  rank  among  them;  in  the  normal  state 
it  is  a  constituent  of  the  anatomical  elements,  but  not  of  the 
llnids.  In  the  economy  of  the  living  animal  a  measured  quan- 
tit}r  of  toxic  substance  exists  in  a  state  of  combination  in  the 
cellular  elements,  and  it  is  only  by  an  abnormal  modification  of 
these  elements  that  we  see  their  poisons  come  into  the  lluids. 
The  fluids  contain  notably  only  the  exact  quantity  of  potass 
which  they  carry  to  the  tissues  or  to  the  emunctories;  the 
potass,  therefore,  is  only  on  its  transit  in  these  fluids. 

The  mineral  and  organic  poisons  are,  therefore,  in  general, 
poisons  of  disassimilation  ;  but  in  the  organs  whose  disassimi- 
lation produces  poisons  there  are  those  which  liberate  a  part  of 
the  material  of  which  they  are  composed,  immediately  it  is  free, 
into  particular  canals,  which  conduct  it  to  the  exterior,  e.g.,  the 
glands  of  the  skin,  the  liver. 

(83) 


84  LECTURES   ON    AUTO-INTOXICATION. 

Bile  escapes  direct  absorption  by  the  blood,  but  not  all  con- 
tact with  it,  since  at  the  surface  of  the  intestine  it  is  in  contact 
with  the  mesenteric  capillaries ;  only  the  liver  is  still  there  to 
seize  it  anew  and  to  throw  it  out  again  into  the  intestine. 

Would  bile  be  dangerous  to  the  blood  ?  Assuredly  ;  its  tox- 
icity  is  less  than  is  believed,  but  it  is  still  considerable. 

In  an  experiment  of  Vulpiau  we  see  that  10  grammes  of  bile 
per  kilogramme  of  animal  constitute  a  poisonous  dose.  We  even 
see  it  kill  with  4,  5,  or  6  grammes  one  kilogramme  of  animal.  Bile 
is,  therefore,  at  least  five  times  (occasionally  ten  times)  more 
toxic  than  urine.  The  small  size  of  the  gall-bladder  and  the  small 
quantity  of  bile  which  we  find  in  it  post-mortem  would  lead  us 
to  believe  that  this  secretion  is  of  little  importance.  We  change 
that  opinion  when  we  know  the  quantity  of  bile  secreted  in 
twent3r-four  hours.  According  to  Beaunis,  we  may  value  at 
about  1  kilogramme  the  quantity  of  bile  produced  in  twenty- 
four  hours  in  man.  From  observation  in  cases  of  biliary  fistulae, 
Ran'ke  found  a  mean  of  14  grammes  of  bile  per  kilogramme  of 
living  weight  for  twenty-four  hours.  Von  Wittich  has  obtained 
from  such  in  a  woman,  in  twenty-four  hours,  528  cubic  centi- 
metres ;  and  in  a  woman  equally  suffering  from  fistula  of  the  gall- 
bladder, with  complete  obliteration  of  the  gall-duct,  I  have  seen 
the  daily  quantity  of  the  bile  reach  800  grammes.  Thus,  if,  in 
equal  time,  the  urine  eliminates  half  of  that  which  would  kill  a 
man,  bile  eliminates  thrice  the  quantity.  The  total  quantity  of 
bile  is  six  times  more  toxic  than  the  totality  of  urine. 


COMPARISON   BETWEEN   THE   TOXICITY   OF   BILE   AND 
THAT    OF    URINE. 

A  man  of  65-70  kilogrammes  eliminates  in  twenty-four  hours 
1350  cubic  centimetres  of  urine  on  an  average,  or  about  20 
grammes  of  urine  per  kilogramme.  This  urine  can  kill  an 
animal  of  1  kilogramme  after  a  dose  of  45  cubic  centimetres. 
Man,  for  each  kilogramme  of  his  body-weight,  eliminates,  there- 
fore, in  twenty-four  hours,  by  his  urine,  sufficient  to  kill  10U^X20_. 
444  grammes  of  living  matter.  A  man  of  37  kilogrammes  elim- 
inates in  twenty-four  hours  652  cubic  centimetres  of  bile ;  that 
is,  13.45  cubic  centimetres  per  kilogramme.  This  bile  can  kill 


TOXICITT   OF   BILE   AND   THAT   OF    URINE.  85 

an  animal  of  1  kilogramme  at  the  doge"  of  5  cubic  centimetres. 
Man,  for  each  kilogramme  of  his  body-weight,  eliminates,  there- 
fore, in  twenty-four  hours,  by  bile,  sufficient  to  kill  -J^~  =  2690 
grammes  of  living  matter.  From  what  precedes  we  may  con- 
clude (1)  that  1  kilogramme  of  living  matter  being  killed  by 
5  cubic  centimetres  of  bile  and  by  45  cubic  centimetres  of  urine, 
bile  is  nine  times  more  toxic  than  urine ;  (2)  that  the  quantity 
of  bile  secreted  in  twenty-four  hours  by  1  kilogramme  of  man 
being  capable  of  killing  2690  grammes  of  living  matter,  whilst 
the  quantity  of  urine  secreted  by  1  kilogramme  of  man  in 
twenty-four  hours  is  capable  of  killing  only  444  grammes  of 
living  matter,  the  toxic  activity  of  the  hepatic  secretion  is  six 
times  greater  than  the  toxic  activity  of  the  renal  secretion. 
^-==6.  If  all  the  bile  which  the  liver  secretes  passed  directly 
into  the  blood,  man  would  be  poisoned  by  his  own  bile  in  eight 
hours  fift3'-five  minutes.  If  all  the  urine  that  the  kidneys 
secreted  passed  directly  into  the  blood,  man  would  be  poisoned 
by  his  own  urine  in  two  days,  six  hours,  and  thirty -two  minutes. 


We  see  the  danger  which  results  either  from  any  impediment 
placed  in  the  way  of  the  elimination  of  bile  or  from  its  absorp- 
tion. Fortunately,  more  than  one-half  is  eliminated  in  twenty  - 
four  hours  by  the  digestive  canal ;  the  water  of  the  faeces  repre- 
sents the  water  of  400  grammes  of  bile.  Besides,  the  other  half 
of  the  bile  is  not  absorbed,  for  if  it  was  eliminated  by  the  urine  the 
toxicity  of  urine  would  be  much  more  considerable,  We  would  be 
obliged  to  admit  that  the  urine  of  twenty-four  hours  was  capable 
of  killing  the  whole  individual,  or  even  twice  the  individual ;  but 
experiment  has  shown  us  that  urine  has  not  this  toxicity. 

What  becomes,  then,  of  this  half  of  the  bile  which  is  not 
thrown  out  by  the  digestive  canal  ?  Does  the  liver  destro}-  it? 
Do  the  tissues  change  it?  These  two  hj'potheses  are  possible, 
but  not  demonstrated. 

What  is  demonstrated  is,  that  in  the  intestine  a  portion  of 
the  bile  ceases  to  be  absorbable.  The  coloring  matter  and  the 
biliary  suits  are  metamorphosed, — precipitated  or  rendered  insol- 
uble. Yet,  in  certain  morbid  conditions,  bile  may  be  absorbed 
in  the  liver  itself,  at  the  margin  of  the  hepatic  cells.  In  these 
cases,  if  the  kidneys  remain  permeable,  it  becomes  a  menace  to 


86  LECTURES   ON   AUTO-INTOXICATION. 

intoxication ;  if  they  have  ceased  to  be  so,  poisoning  is  the 
result.  If  the  kidney  has  remained  permeable,  and  no  general 
accidents  have  arisen,  the  urine  becomes  toxic, — not  to  the  indi- 
vidual himself,  but  to  the  animals  upon  which  we  experiment. 
Certain  jaundiced  urines  are  toxic  at  the  rate  of  13  cubic  centi- 
metres per  kilogramme  ;  these  urines  owe,  without  doubt,  a  great 
part  of  their  toxicity  to  the  presence  of  coloring  matters,  since, 
once  decolorized,  they  may  be  injected  in  double  or  triple  the 
quantity  ;  but  the  destruction  of  the  blood-globules  and  hepatic 
cells,  the  products  of  increased  disassimilation,  which  the 
rapid  diminution  in  weight  amongst  jaundiced  people  bears 
witness  to,  and  especially  the  potass,  contribute  to  rendering 
jaundiced  urines  very  toxic. 


INTRA- VENOUS  INJECTION   OF   A   HIGHLY-JAUNDICED  URINE. 

March  11,  18S5.  Into  a  rabbit  weighing  1650  grammes  we 
injected  22  cubic  centimetres  of  a  very  pronounced  jaundiced 
urine,  coming  from  a  patient  in  the  Saint  Landry  Ward  (Hopital 
Lariboisiere),  who  was  passing  900  grammes  of  it  in  twenty-four 
hours.  After  the  sixth  cubic  centimetre,  agitation.  At  the 
ninth  cubic  centimetre,  pupil  in  great  part  contracted.  At  the 
fifteenth  cubic  centimetre,  pupil  pin-point;  spasms;  hurried 
respiration.  At  the  twentieth  cubic  centimeti'e,  screams ; 
spasms.  At  the  twenty-second  cubic  centimetre,  death, — the 
heart  still  beating.  The  animal  received  13  cubic  centimetres 
per  kilogramme. 

INJECTION   OF   THE   SAME   URINE   DECOLORIZED,   IN   NEARLY 
TRIPLE   QUANTITY. 

We  completely  decolorized,  by  means  of  animal  charcoal,  a 
portion  of  the  urine  which  served  for  the  preceding  experiment. 
We  injected  into  the  veins  of  the  ear  of  a  rabbit  weighing  1680 
grammes  50  cubic  centimetres  of  this  urine.  The  injection  was 
driven  in  pretty  rapidly.  At  the  twenty-seventh  cubic  centi- 
metre, slight  tonic  shaking, — stronger  at  the  forty-first  cubic 
centimetre.  At  the  forty-eighth  cubic  centimetre,  spasms, — not 
ceasing  even  at  the  fiftieth  cubic  centimetre.  At  this  moment 
tonic  convulsions,  with  opisthotonos.  Respiration,  which  had 
become  rapid  after  the  twenty-fifth  cubic  centimetre,  stopped  ; 
but  the  animal  returned  to  life.  At  no  moment  had  the  pupil 
been  contracted.  The  rabbit  had  received  SO  cubic  centimetres 


PUTREFACTIVE  INTOXICATION.  87 

per  kilogramme.  On  the  12tli  of  March  the  rabbit  had  diarrhoea 
and  much  albumen  in  its  urine.  On  the  14th  of  March  it  was 
quite  well. 

INTRA-VENOUS  INJECTION   OP  JAUNDICED  URINE. 

March  14,  1885.  Forty -five  cubic  centimetres  of  urine  from 
the  same  patient  whose  urine  had  served  for  the  preceding 
experiments  were  injected  into  a  rabbit  weighing  1450  grammes. 
Spasms  commenced  after  12  cubic  centimetres.  At  20  cubic 
centimetres  the  pupil  began  to  contract.  At  42  cubic  centi- 
metres it  was  ptinctiform.  Spasms  began  and  death  came  after 
45  cubic  centimetres,  or  31  cubic  centimetres  per  kilogramme. 

INJECTION   OF   NEARLY    DOUBLE  QUANTITY   OF   SAME 
DECOLORIZED   URINE. 

Into  a  rabbit  weighing  1300  grammes  we  injected  70  cubic 
centimetres  of  the  preceding  urine,  decolorized  by  means  of 
carbon.  Spasm  came  on  after  68  cubic  centimetres.  The  pupil 
was  not  contracted.  Death  came  after  the  seventieth  cubic 
centimetre.  That  was  54  cubic  centimetres  per  kilogramme. 


If  bile  is  toxic  directly  and  indirectly,  the  intestine  is  already 
far  as  bile  is  concerned — a  source  of  intoxication, — in  as 
feeble  a  proportion  as  we  please,  but  still  really  so.  From  there 
pass  onward  into  the  blood,  in  addition,  other  materials  which 
are  eliminated  by  the  urine, — mineral  salts  (e.gr.,  potass)  intro- 
duced by  the  food,  and  other  toxic  substances  of  alimentary 
origin.  Nevertheless,  this  is  only  a  minimum  portion  of  the 
poisons  which  the  blood  may  derive  from  the  intestinal  canal. 

There  is  a  third  source  of  intoxication  for  the  blood  ;  it  is 
putrefaction :  not  only  that  which  arises  from  the  imperfect 
metamorphosis  of  digested  matter,  but  that  which  the  presence 
of  micro-organisms  in  the  intestinal  tube  incessantly  maintains. 
In  the  digestive  canal  the  conditions  most  favorable  for  the 
elaboration  of  poisons  are  realized.  Therein  are  found  nitrog- 
enous substances,  already  peptonized  ;  and  peptones  are,  as  you 
know,  excellent  culture-media  for  microbes.  They  are  in  asso- 
ciation with  a  notable  quantity  of  water  in  a  tube  at  a  constant 
temperature  of  37  degrees.  The  digestive  canal  is  constantly 


88  LECTURES   ON   AUTO-INTOXICATION. 

open  exteriorly.  Besides,  the  foods  taken  carry  in  with  them 
putrefactive  agents ;  respiration  allows  of  the  deposition  of 
dust  in  the  pharynx,  which,  with  each  movement  of  degluti- 
tion, is  caught  by  the  saliva,  along  with  the  micro-organisms 
which  it  conceals.  The  conditions  favorable  for  the  mainte- 
nance of  putrefaction  are  so  numerous  that  we  ask  whether 
digestion  can  ever  go  on  normally.  Fortunately,  the  organism 
secretes  in  the  stomach,  on  the  introduction  of  food,  a  juice 
which  is  opposed  to  all  fermentation.  Experimentally,  we  know 
that  1.10  grammes  of  anhydrous  hydrochloric  acid  per  litre  pre- 
vents all  fermentation  ;  but  the  gastric  juice  contains  more.  We 
find  therein,  per  litre,  up  to  3.30  grammes,  and  even  5  grammes, 
of  hydrochloric  acid,  estimated  as  the  fuming  acid  of  commerce. 

But  infectious  agents  have  not  been  destroyed  by  the  gastric 
juice  in  the  stomach ;  they  have  only  been  neutralized ;  they 
have  only  passed  into  a  state  of  latent  vitality.  The  action  of 
organized  ferments  re-commences  when  the  foods  have  passed 
through  the  pylorus.  The  acid  of  the  gastric  juice  finds  itself 
at  this  moment  neutralized  by  the  alkalies  of  the  intestine, 
whose  contents,  if  not  alkaline  or  neutral,  are  in  every  case  only 
feebly  acid  by  a  commencement  of  acetic  fermentation. 

We  have  regarded  the  bile  as  capable  of  prolonging  the 
arrest  of  fermentations ;  but  bile  is  capable  of  undergoing  fer- 
mentation itself,  or  of  putrefying.  It  can,  therefore,  only  feebly 
oppose  fermentation  in  the  small  intestine.  At  any  rate,  it  can 
have  no  influence  upon  those  which  are  actively  carried  on  in 
the  large  intestine. 

Thus  do  we  find  the  small  intestine,  on  the  one  hand,  and  the 
large  intestine  particularly,  on  the  other,  capaple  of  passing 
products  of  putrefaction  into  the  blood.  But,  are  the  putrid 
substances  toxic?  Haller  believes  they  are  not.  Gaspard,  in 
1822,  established  the  fact  that  putrid  substances  are  toxic,  and 
that  they  are  actually  more  so  than  substances  arising  from 
disassimilation.  He  injected  into  the  veins  of  animals  liquid 
arising  from  putrefaction  of  blood  or  of  meat.  He  induced 
faintness,  diarrhoea,  and  vomitings  ;  hyperaemia  of  mucous  mem- 
branes; then  death;  and  at  the  autopsy  ecchymoses  of  the 
digestive  canal  were  seen ;  also  of  the  cellular  tissues, — those 


PUTREFACTIVE  INTOXICATION.  89 

of  the  muscles  and  of  the  heart;  swelling  of  the  spleen  and 
the  mesenteric  glands ;  congestion  of  the  lungs, — phenomena 
all  of  which  were  verified  by  those  who  have  since  repeated 
Gaspard's  experiments. 

Magendie  has  studied  intoxication  by  gases  from  the  basins 
of  water-closets, — he  had  previous  knowledge  of  the  morbid 
influence  of  putrid  emanations. 

The  experiments  of  Gaspard  have  been  regarded  as  correct 
by  Panum,  Bergmann,  and  Billroth.  It  yet  remains  to  be  known 
whether  the  facts  observed  by  Gaspard  arose  from  intoxication 
or  infection.  So  far  as  he  is  concerned,  he  could  not  distinguish 
putrefaction  from  infection,  not  having  any  knowledge  of  infec- 
tious agents.  He  injected  into  the  blood  of  animals  the  prod- 
ucts of  the  life  of  inferior  organisms,  and  at  the  same  time  these 
organisms  themselves.  At  one  and  the  same  time,  therefore,  he 
caused  intoxication  and  infection. 

Panum  tried  to  solve  this  difficulty.  By  boiling  at  100°  C. 
he  destroj'ed  the  organisms  themselves  before  injecting  the  prod- 
ucts of  putrefaction,  and  he,  too,  observed  the  same  phenomena. 

Koch  has,  besides,  furnished  another  argument.  If  it  is  a 
question  of  intoxication,  the  effects  produced  ought  to  be  imme- 
diate and  proportional  to  the  quantity  of  putrid  matter  injected. 
If  it  is  one  of  infection  a  period  of  incubation  is  necessarj*, 
and  the  quantit}r  ought  not  to  seriously  influence  the  accidents 
which  follow.  Experiment,  however,  shows  that  in  those  cases 
the  accidents  happen  immediately  after  the  injection  of  the 
putrid  material.  If  we  inject  small  quantities  of  it,  we  have 
accidents  less  grave  than  from  large  quantities. 

Thus,  the  absence  of  incubation  and  the  proportional  ratio  of 
accidents  to  the  quantity  of  poison  decide  the  question  of  their 
nature ;  they  are  truly  of  the  order  of  intoxications.  It 
remains,  now,  to  isolate  the  toxic  substances  produced  by  the 
lower  organisms. 


LECTURE   IX. 

ORIGIN  OF  THE  Toxic  SUBSTANCES  OF  URINE — TOXICITY  OF  THE 
PRODUCTS  OF  PUTREFACTION  AND  OF  THE  FAECES. 

Toxicity  of  the  products  of  putrefaction  in  general.  The  accidents  which  they 
determine  belong  to  the  order  of  intoxications.  Attempts  to  isolate  the 
various  products  of  putrefaction. Panum,  Hemmer.  The  sepsine  of  Berg- 
maun  and  Schmiedeberg.  Multiplicity  of  the  alkaloids  of  putrefaction. 

Zulzer  and  Sonnensteiu,  Selmi,  A.   Gautier,  Brouardel,  and  Boutmy. 

Variability  of  the  products  of  putrefaction,  according  to  temperature.  Dim- 
inution of  the  toxicity  of  putrid  substances  owing  to  filtration  through  char- 
coal.  Enumeration  of  the  toxic  substances  which  putrefaction  causes  in 

vitro, — acetic  acid,    butyric,  valeric,   sulphuric,  ammonia,  leucin,  tyrosin, 

indol,  skatol,  cresol,  phenol,  hydrocarbons,  etc. All  these  bodies  exist 

also  in  the  putrefactions  induced  in  the  interior  of  the  digestive  canal.    They 

contribute  to  rendering  the  faeces  toxic. Demonstration  of  the  toxicity  of 

faeces.  Stich.  My  researches  upon  the  alkaloids  of  faeces  ;  their  multi- 
plicity and  their  chemical  characters.  Intra-veuous  injections  of  the  extracts 
of  faeces.  Aqueous  and  alcoholic  extract.  Extract  of  fasces  deprived  of  their 
mineral  substances. Resume  of  the  sources  of  toxicity. 

IT  is  proved  that  putrefaction  gives  birth  to  poisons  whose 
effects  are  revealed  in  the  putrid  fever  of  Gaspard.  We  have 
wondered  if  death,  in  the  cases  which  he  observed,  was  really 
the  result  of  intoxication.  It  is  not  explained  by  embolism,  for 
we  find  neither  the  clinical  character  nor  the  lesions  of  such. 
Was  it,  then,  a  question  of  infection?  Putrefaction,  including, 
as  it  does,  infectious  agents  and  their  products,  we  introduce  all 
at  once  when  we  make  injections  of  putrid  substances.  The 
results  obtained  are  capable  of  being  attributed  to  infectious 
accidents  just  as  much  as  to  toxic  phenomena.  The  disease 
may  be  explained  by  multiplication  in  the  blood  of  micro-organ- 
isms acting  in  accordance  with  one  of  the  five  methods  which 
are  proper  to  them.  To  this  objection  the  experiment  of  Panum 
replies,  for  he  only  injected  putrid  matter  after  having  heated  it 
to  100  degrees ;  and  he,  also,  observed  the  same  phenomena  as 
Gaspard. 

Hiller  introduced  into  the  blood  filtered  putrid  matter  no 
(90) 


TOXICITY   OF   PRODUCTS   OF   PUTREFACTION.  91 

longer  containing  any  figured  corpuscle  visible  under  the  micro- 
scope ;  he  observed  the  same  phenomena.  Besides,  I  have 
recalled  to  you  the  theoretical  argument  of  Koch, — if  it  was  a 
question  of  infection,  a  period  of  incubation  would  be  necessary 
in  order  that  pathogenic  organisms  might  have  time  to  multiply 
in  the  circulation.  The  microbes  which  are  the  most  rapid  in 
their  development  require  twenty  minutes  in  order  that  one 
of  them  can  give  birth  to  two  others.  Besides,  one  microbe 
alone  being  quite  sufficient  theoretically  to  bring  about  infectious 
disease,  a  most  minute  quantity  ought  to  be  sufficient  to  produce 
the  most  severe  accidents.  We  only  know  that  the  pl^siologi- 
eal  effects  are,  in  these  cases,  proportional  to  the  mass  of  toxic 
matter  introduced  into  the  organism. 

The  toxicity  of  the  products  of  putrefaction,  taken  generally, 
being  once  established,  we  ought  to  try  to  isolate  each  one 
of  them.  Panum,  in  1856,  made  the  first  attempt  at  isolation. 
He  evaporated  to  dryness  putrid  matter;  exhausted,  by  alcohol, 
the  dry  residue;  evaporated,  by  boiling,  the  alcohol  from  the 
alcoholic  solution,  and  had  thus  two  extracts, — the  alcoholic 
extract  and  the  residue,  insoluble  in  alcohol,  which  would  be  the 
aqueous  extract.  Redissolving  in  water  the  two  extracts,  he 
studied  comparatively  the  effects  which  each  one  might  produce 
upon  the  living  organism.  He  established  thus  the  fact  that 
the  alcoholic  extract  is  very  feebly  toxic ;  it  represented  one- 
fifth  of  the  total  toxicity.  The  substances  insoluble  in  alcohol 
represent,  consequently,  the  four-fifths  of  that  toxicity. 

Ten  3'ears  later  Heminer  showed  that  putrid  poison  is  in- 
soluble in  alcohol. 

In  1868  Bergmann  and  Schmiedeberg  made  researches  upon 
the  chemical  character  of  the  substances  which  cause  putrid 
material  to  be  toxic.  They  obtained  a  crystallizable  bod}-,  com- 
parable chemically  to  vegetable  alkaloids,  combining  with  acids 
to  form  crystallizable  salts,  and  producing  the  same  physiologi- 
cal effects  as  the  injection  of  putrid  matter.  They  have,  there- 
fore, considered  it  proper  to  ascribe  to  this  body  a  role  in  the 
production  of  toxic  accidents.  This  sepsine,  as  they  called  it, 
has  been  incriminated,  since  then,  by  surgeons,  as  the  cause  of 
certain  complications  of  wounds  (pyaemia,  etc.).  But  already 


92  LECTURES  ON   AUTO-INTOXICATION. 

the  experimenters  of  whom  I  have  spoken  had  recognized,  by 
the  side  of  this  sepsine,  other  bodies  having  a  different  toxicity. 

In  1869  Zulzer  and  Sonnenstein  had  signaled  out  the  presence 
of  alkaloids  in  the  products  of  putrefaction,  having  chemical 
reactions  comparable  to  those  of  atropine,  having  the  property 
of  dilating  the  pupil  and  of  accelerating  the  heart, — alkaloids 
which  also  exist  (as  I  showed  in  1882)  in  the  extracts  of  the 
urine  of  patients  attacked  with  typhoid  fever. 

In  1871  Selmi  again  extensively  resumed  the  study  of  the 
question  of  the  very  numerous  alkaloids  of  putrefaction,  as  well 
as  Gautier  in  1872,  Brouardel  and  Boutmy  in  1880,  devoting 
their  time  to  the  study  of  the  alkaloids  of  the  cadaver. 

The  result  of  all  these  researches  is  that  numerous  alkaloids, 
variously  toxic,  are  developed  in  the  course  of  the  putrefaction 
of  organized  substances.  A  putrid  mass,  taken  en  bloc,  has  a 
very  variable  toxicity.  Its  toxicity  increases  more  and  more 
in  proportion  as  putrefaction  advances.  After  the  first  products 
of  the  transformation  of  organized  matter  are  destroyed,  the 
toxicity,  Avhich  has  been  at  length  increasing  in  it,  afterward 
diminishes,  and  becomes  annihilated  at  the  end  of  a  certain  time. 
Putrefaction  by  heat  develops  a  more  intense  toxicit}' ;  by  cold, 
it  is  not  only  slower,  but  modified  also  in  its  intensity,  as  the 
following  experiment  proves. 

As  certain  toxic  organic  substances  lose  a  part  of  their  tox- 
icity after  having  been  filtered  through  charcoal,  I  have  caused 
putrid  substances  to  be  filtered.  These  lose  a  large  part  of  their 
toxicity  by  this  means. 


INTRA-VENOUS  INJECTION   OP   AN   AQUEOUS   EXTRACT   OF   MUSCLE 
PUTREFIED   IN   THE   COLD. 

April  30,  1885.  We  macerated,  in  the  cold,  500  grammes  of 
muscle  in  500  grammes  of  water  for  twenty-four  hours.  We 
pressed  it;  we  obtained  502  cubic  centimetres  of  a  distinctly 
colored  liquid,  and  filtered  it.  We  injected  into  a  rabbit  weigh- 
ing 1850  grammes  50  cubic  centimetres  of  this  liquid,  or  27 
cubic  centimetres  per  kilogramme.  We  observed  a  medium  my- 
osis  and  great  depression.  The  liquid  was  not  sufficient  to  allow 
of  a  larger  injection. 


TOXICITY   OF   PRODUCTS   OP   PUTREFACTION.  93 

INTRA-VENOUS  INJECTION   OF   AN   AQUEOUS   EXTRACT   OF   MUSCLE 
PUTREFIED  BY   HEAT. 

M:iy  5,  1885.  1.  We  macerated  1200  grammes  of  muscle  in 
1200  grammes  of  water,  in  a  stove,  for  two  days.  The  liquid, 
strongly  colored  red,  was  filtered.  Into  a  rabbit  weighing  1720 
grammes  we  injected  40  cubic  centimetres  of  this  liquid.  Death 
supervened,  with  dyspnoea  and  convulsions,  but  with  little  my- 
osis,  after  a  dose  of  23.25  cubic  centimetres  per  kilogramme. 

2.  We  decolorized,  by  means  of  charcoal,  a  certain  quantity 
of  this  same  liquid.  Into  a  rabbit  of  1480  grammes  we  injected 
100  cubic  centimetres.  Death  supervened,  with  slight  convul- 
sions and  myosis.  The  animal  received  67.56  cubic  centimetres 
per  kilogramme. 


The  pupillary  contraction  which  the  injection  of  normal  urine 
causes  is  also  produced  by  the  injection  of  putrid  material, 
even  though  it  has  been  filtered  through  charcoal.  The  toxicity 
of  these  substances  is,  therefore,  due  to  another  substance  than 
that  which  exists  in  normal  urine,  since  this,  filtered  through 
charcoal,  loses  its  power  of  causing  contraction  of  the  pupil. 

These  researches  are  still  only  on  the  surface,  so  to  speak.  We 
have,  at  length,  seen  putrid  intoxication  in  its  entirety  ;  we  have 
afterward  studied  certain  isolated  parts  of  it.  The  alkaloids 
have  been  studied  with  some  care ;  but  the  toxicity  of  putre- 
factive products  is  due  to  other  causes  than  alkaloids.  There  is 
3ret  another  series  of  toxic  substances  which  putrefaction  causes. 

The  acids,  —  acetic,  butyric,  valeric,  sulphuric, — ammonia 
and  the  ammonia  compounds,  leucin,  leuceine,  tyrosin,  indol, 
skatol,  cresol,  phenol,  and  the  hydrocarbons  are  all  toxic.  All 
may  and  do  contribute,  in  their  part,  to  the  toxicity  of  putrid 
substances,  taken  en  bloc. 

All  that  has  just  been  said  of  putrefaction  in  vitro  is  appli- 
cable to  putrefaction  in  the  digestive  tracts ;  for  the  digestive  canal 
is  a  veritable  putrefactive  apparatus.  Moisture,  heat,  and  the 
germs  coining  from  the  atmosphere  concur  in  producing  putre- 
faction as  soon  as  the  hydrochloric  acid  or  the  bile  has  disap- 
p(  :i  red  or  become  changed  in  its  nature.  The  alimentary  residues 
which  have  not  been  digested  and  the  peptones  not  yet  absorbed 
are  transformed,  without  any  alteration,  into  infectious  agents. 


94  LECTURES   ON   AUTO-INTOXICATION. 

Theoretically,  in  the  second  and,  particularly,  in  the  third  parts 
of  the  intestine,  there  ought  to  occur  the  same  phenomena,  and 
the  same  bodies  should  develop  which  chemistry  has  revealed  in 
experimental  putrefaction.  In  fact,  we  find  in  faecal  matter  the 
alkaloids  of  putrefaction  (as  I  have  shown,  in  1882).  They  may 
develop  there  even  under  the  influence  of  a  ferment  which  is  not 
organized, — trypsine.  Since  1881  Tanret  has  seen  that  ether  and 
soda  carry  into  the  peptones  some  substances  having  the  char- 
acters of  alkaloids,  and  which,  in  spite  of  certain  analogies  in 
chemical  reaction,  differ  already  from  peptones  by  their  solubility 
in  ether.  In  1883  Brieger  demonstrated  that  alkaloids  are  devel- 
oped during  the  act  of  peptonization.  Faecal  matter  contains  also 
excretine,  whose  presence  and  toxicity  Marcet  has  drawn  atten- 
tion to.  Strong  as  was  the  presumption  in  favor  of  the  toxicity 
of  faecal  substances,  it  was  yet  necessaiy  to  demonstrate  it  briefly. 

In  1853  Stich  showed  that  faecal  matter  is  toxic,  but  not  to 
the  individual  who  has  produced  it ;  because  this  experimenter 
introduced  into  the  intestine  of  one  animal  the  faecal  matter  of 
another.  In  reality,  faecal  matter  is  toxic,  in  a  general  way,  to 
living  cells.  If  we  seek  for  those  elements  to  which  the  toxicity 
of  faecal  matter  is  due,  we  have  only  the  embarrassment  of  choice. 
I  will  insist  upon  the  alkaloids  whose  existence  I  demonstrated 
in  September,  1882.  I  made  extracts  by  means  of  chloroform 
and  by  ether,  after  having  rendered  faecal  matter  alkaline. 

I  arrived  at  this  conclusion,  that  faecal  matter  contains  various 
alkaloidal  substances,  some  soluble  in  ether  and  insoluble  in  chlo- 
roform, others  insoluble  in  ether  and  soluble  in  chloroform.  All 
have  the  characters  of  alkaloids,  behaving  like  them  under  the 
iodo-iodurated  reagent,  double  iodide  of  mercury  and  potassium, 
phospho-molybdate  of  soda,  tungstate  of  soda,  and  tannin.  I 
have  isolated  them  in  notable  quantities,  but  insufficient  to  pro- 
duce intoxication.  I  believe,  therefore,  that  putrefaction  plays 
a  part  in  the  toxicity  of  faecal  substances,  but  less  than  is  sup- 
posed. I  have  practiced  intra-venous  injection  with  the  extracts 
of  faecal  matter. 

The  aqueous  extract  is  toxic.  It  produces  depression  and 
diarrhoea, — phenomena  the  precursors  of  death.  But  it  is  chiefly 
the  alcoholic  extract  which  is  energetically  toxic  in  small  doses. 


TOXICITY   OF   FAECAL   MATTER.  95 

I  have  seen  the  alcoholic  extract  from  1 7  grammes  of  faecal  mat- 
ter kill,  having  induced  severe  convulsions.  Now,  man  forms, 
in  twenty -four  hours,  400  grammes  of  faecal  matter.  We  can 
seek  for  that  substance  to  whose  presence  is  due  this  toxicity 
of  the  faeces.  The  extract  of  faecal  matter,  when  it  is  deprived 
of  its  mineral  substances,  salts  of  potass,  and  ammonia,  when 
it  has  been  reduced  to  dryness,  taken  up  again  with  absolute 
alcohol,  treated  by  an  alcoholic  solution  of  tartaric  acid,  filtered, 
neutralized  by  sodium  carbonate,  evaporated,  taken  up  again  by 
alcohol,  dried  anew,  and  taken  up  by  water,  only  kills  in  doses 
infinitely  larger.  It  is  no  longer  the  extract  from  39  gi-ammes 
of  faecal  matter  that  we  must  inject  to  induce  toxic  and  fatal 
accidents,  but  the  extract  of  298  grammes. 


INTR A- VENOUS    INJECTION    OF   EXTRACT    OF    F.SCAL    MATTER    AND    OF 
THE    SAME    EXTRACT   DEPRIVED   OF  MINERAL    SUBSTANCES. 

April  28th.  We  collected  on  April  23d  600  cubic  centimetres 
of  faecal  matter,  which  we  exhausted  with  1  litre  of  absolute  alco- 
hol. The  alcohol  was  filtered  and  distilled.  The  residue  was  taken 
up  by  225  cubic  centimetres  of  absolute  alcohol.  We  afterward 
divided  the  liquid  into  two  parts, — one  of  150  cubic  centimetres, 
representing  400  grammes  of  faecal  matter;  the  other,  75  cubic 
centimetres,  representing  200  grammes  of  faecal  matter.  A.  The 
second  part  (200  grammes)  was  distilled  and  taken  up  by  water. 
After  filtration  we  obtained  90  cubic  centimetres  of  liquid,  of 
which  1  cubic  centimetre  represented  2.22  grammes  of  fecal 
matter.  Into  a  rabbit  of  1850  grammes  we  injected  33  cubic 
centimetres  of  this  liquid.  At  this  moment  convulsions,  death. 
That  is,  17.8  cubic  centimetres  per  kilogramme,  or  the  ex- 
tract of  39.5  grammes  of  faecal  matter.  B.  The  first  part  (400 
grammes)  was  distilled  and  taken  up  by  absolute  alcohol.  We 
precipitated  the  potass  and  ammonia  by  tartaric  acid.  We  also 
neutralized,  after  filtration  by  sodium  bicarbonate,  filtered,  evap- 
orated, and  took  up  by  absolute  alcohol.  Again  we  filtered, 
evaporated,  and  took  up  by  distilled  water,  and  then  filtered. 
We  obtained  35  cubic  centimetres  of  liquid,  of  which  1  cubic 
centimetre  represented  13.4  grammes  of  faecal  matter.  Into  a 
rabbit  of  1340  grammes  we  injected,  by  an  intra-venous  channel, 
35  cubic  centimetres.  No  phenomena  were  observable.  The 
rabbit  received  400  grammes  of  faecal  matter,  or  the  extract  of 


id  4UU   g 

offeecal 


298  grammes  offeecal  matter  per  kilogramme. 


96  LECTURES  ON   AUTO-INTOXICATION. 

We  may,  therefore,  consider  the  following  as  contributing  to 
the  toxicity  of  the  fseces  :  on  the  one  hand,  potass  and  ammonia 
chiefly ;  on  the  other,  something  which  is  soluble  in  alcohol,  and 
which  is  neither  potass  nor  ammonia ;  then  bile,  and,  lastly,  the 
residues  of  putrefaction. 

To  sum  up :  the  aqueous  extract  of  putrid  matter  is  very 
toxic,  that  of  faecal  matter  is  slightly  so  ;  the  alcoholic  extract 
of  putrid  matter  is  not  very  toxic,  that  of  faecal  matter  is 
decidedly  so. 

If  we  class  toxic  products  together,  we  place  in  the  first  line 
mineral  substances, — chiefly  potass, — alimentary  products,  or 
those  furnished  by  disassimilation ;  in  the  second  line  the  prod- 
ucts of  intestinal  putrefaction,  amongst  which  ammonia  occu- 
pies an  elevated  position ;  in  the  third  line  the  organic  products 
of  disassimilation,  and  therein  is  included  a  small  quantity  of  bile, 
which  may  be  re-absorbed  by  the  intestinal  mucous  membrane. 

Thus  we  recognize  all  the  sources  of  the  toxic  materials  of 
the  economy, — the  tissues,  secreting  organs,  foods,  putrefactions. 

The  toxic  products  coming  from  these  four  seats  of  origin, 
introduced  into  the  blood,  give  to  it  that  slight  degree  of  tox- 
icity which  we  have  been  able  to  estimate.  The  blood  imposes 
this  toxicity  upon  the  products  of  secretion,  and  especially  upon 
the  renal  emunctory.  After  having  demonstrated  that  the  urine 
is  toxic,  I  showed  that  it  cannot  be  otherwise.  The  blood  is 
not,  to  any  extent,  habitually  toxic,  because  urine  is  strongly 
so ;  if  this  were  no  longer  toxic  the  blood  would  become  toxic, 
since  poisons  are  always  being  introduced  into  it,  proceeding 
from  disassimilation,  from  foods,  the  products  of  intestinal 
putrefaction,  and  the  products  of  secretion. 

We  never  observe  accidents  the  outcome  of  intoxication 
with  normal  kidne}^ ;  if  the  kidneys  are  diseased  the  individual 
dies.  To  all  cases  of  death  arising  from  suppression  of  the 
renal  function  we  apply  the  term  uraemia.  But  what  we  already 
know  enables  us  to  foresee  that  a  complexity  of  phenomena  is 
hidden  under  this  name. 


LECTURE   X. 

INTESTINAL  ANTISEPSIS. 

Resume  of  the  causes  of  the  toxicity  of  the  contents  of  the  digestive  canal.   Potass 

and  ammonia,  bile,  putrid  substances. Poisons  absorbed  in  the  intestine 

must  traverse  the  blood,  since  they  are  found  in  the  urine.  Parallelism 
between  the  toxicity  of  urine  and  that  of  material  contained  in  the  intes- 
tine. We  can  diminish  the  toxicity  of  urine  by  inducing  disinfection  and 
antisepsis  of  the  digestive  canal. Influence  of  charcoal  taken  in  a  suffi- 
cient quantity  upon  diminution  of  the  toxicity  of  urine. On  intestinal 

antisepsis.  Conditions  which  a  medicament  ought  to  fulfill  when  destined 
to  briug  about  intestinal  antisepsis. Salicylate  of  bismuth,  salts  of  mer- 
cury, iodoform,  naphthalin.  Their  advantages  and  inconveniences.  Method 

of  administering  naphthalin. Charcoal  fixes  the  coloring  matter  and  the 

toxic  products  of  bile.    Naphthalin  is  opposed  to  intestinal  fermentation. 

THE  organism  contains  poisons  the  origins  of  which  we  know, 
viz.,  the  destruction  of  cells,  disassiniilation,  secretion,  ingestion, 
and  putrefaction. 

The  digestive  canal  contains  three  orders  of  these  poisons : 
those  which  come  from  the  ingesta,  bile,  and  putrid  material. 
Its  contents,  therefore,  should  be  toxic.  Experimentation  has 
demonstrated  that  they  are  toxic  from  the  potass  and  ammonia, 
toxic  from  the  bile  and  putrid  material. 

There  are,  therefore,  poisons  in  one  part  of  the  organism 
from  which  absorption  is  continually  taking  place.  Can  this 
absorption  produce  intoxication  ?  We  cannot  demonstrate  ex- 
perimentally that  the  poison  enters  the  blood,  but  we  can  demon- 
strate that  it  leaves  it.  It  is,  therefore,  necessary  to  see  whether 
the  toxicity  of  the  urine  is  in  keeping  with  the  toxicity  of  the 
digestive  tube,  and  as  to  whether  their  variations  are  parallel. 

In  1882,  whilst  demonstrating  the  alkaloids  found  in  normal 
feecal  matter,  I  considered  those  as  the  source  of  nearly  all  the 
alkaloids  of  the  economy.  I  have  been  able  in  one  instance 
to  estimate  their  quantity  as  15  milligrammes  per  kilogramme 
of  faecal  matter.  I  noticed  that  each  time  these  alkaloiclal  sub- 
stances increase  in  the  fneces  they  increase  in  the  urine,  although 
always  smaller  in  quantity.  I  noticed,  too,  that  the  parallelism 
is  preserved  not  only  from  a  quantitative  point  of  view,  but  also 

7  (97) 


98  LECTURES   ON    AUTO-INTOXICATION. 

as  regards  their  nature.  Just  as  there  has  been  a  predominance, 
in  the  digestive  canal,  of  alkaloids  soluble  in  ether  or  those 
which  are  soluble  in  chloroform,  so  have  I  seen  predominate,  in 
like  manner,  one  or  the  other  in  the  urine. 

I  am  less  inclined,  to-day,  to  add  so  much  -importance  to 
these  toxic  products.  We  can  arrive  at  the  same  opinion  by 
taking  toxic  substances  in  their  totality. 

We  may  suppress  a  part  of  the  toxic  matter  of  urine  by 
fixing  that  of  the  intestine  by  means  of  charcoal,  which  retains 
the  coloring  substances  and  the  alkaloids.  This  is  to  induce 
not  antisepsis,  but  disinfection  of  faecal  matter. 

The  extract  of  200  grainmes  of  fsecal  matter,  in  the  case  of 
patients  by  whom  we  have  caused  to  be  ingested  the  required 
quantity  of  charcoal,  is  inoffensive  to  those  animals  into  which 
we  have  injected  it,  whilst  we  killed  with  the  extract  of  17 
grammes,  of  fsecal  matter  not  disinfected,  per  kilogramme.  This 
intestinal  disinfection  by  charcoal  diminishes  also  the  toxicity  of 
urine  by  from  one-half  to  two-thirds.  If  we  wished  to  push  the 
inquiry  further,  it  would  be  necessary  to  produce  antisepsis  by 
preventing  even  the  putrefaction  which  is  produced  in  the 
intestinal  canal. 

It  is  a  long  time  since  we  have  produced  antisepsis  without 
knowing  it,  just  in  the  same  way  as  M.  Jourdain*  made  prose. 
By  giving  calomel,  or  the  black  sulphide,  we  diminish,  without 
knowing  it,  putrefaction.  Many  physicians  have  done  so  con- 
sciously, supposing  that  substances  with  a  putrid  odor  would  be 
offensive  to  the  elements  with  which  they  are  in  contact. 

We  have  employed  chlorine  internally,  and  pure  iodine, — ex- 
cellent antiseptics, — the  sulphites,  hyposulphites,  phenic  acid, 
creasote  (Pecholier),  and  boracic  acid.  We  have  obtained 
nothing  by  these  means  save,  perhaps,  with  the  sulphites  (Sem- 
mola,  Pauli)  and  the  sulphide  of  carbon  (Dujardin-Beaumetz). 

A  reproach  which  at  the  outset  we  can  theoretically  raise 
in  regard  to  all  of  these  substances,  with  the  exception,  perhaps, 
of  the  last  one,  is,  that  they  are  soluble  and  absorbable.  In  the 
long  journey  from  the  mouth  to  the  intestine  the  antiseptic 
agent  loses  some  of  its  power.  One  other  inconvenience  which 

*  This  refers  to  "  Le  Bourgeois  Gentilhoinme  "  of  Moliere. 


INTESTINAL   ANTISEPSIS.  99 

might  arise  from  absorption  of  the  antiseptic  agent  is,  that,  when 
introduced  into  the  blood  in  a  sufficiently  large  quantity,  it 
might  exercise  therein  a  toxic  influence. 

The  conditions  which  a  substance  should  fulfill  when  des- 
tined to  bring  about  intestinal  antisepsis  are,  that  it  should 
not  be  absorbable,  and  yet  should  be  capable  of  being  given  in 
doses  efficaciously  antiseptic  without  inducing  by  itself  any 
toxic  influence  upon  the  organism.  We  must,  therefore,  use 
insoluble  antiseptics. 

Salicylate  of  bismuth  and  iodoform,  extolled  by  Vulpian ; 
naphthalin  (Rossbach)  ;  calomel,  which  is  changed  into  bichloride 
in  the  stomach  and  black  sulphide  in  the  intestine ;  black  sul- 
phide employed  alone  (Serres,  Becquerel),— these  have  each  in 
their  turn  enjoyed  considerable  favor.  A  portion  of  these 
agents  is  always  absorbed. 

Thus,  with  salicylate  of  bismuth  the  faecal  matter  is  black- 
ened owing  to  the  sulphide  of  bismuth,  and  the  urine  contains 
salicylic  acid. 

With  iodoform,  which  I  have  employed  for  a  long  time  now, 
we  find  a  little  iodine  in  the  urine,  and  the  stools  contain  free 
iodoform. 

When  we  administer  naphthalin  the  stools  contain  it.  This 
body,  hitherto  considered  insoluble  in  water,  is  absorbed  to  the 
extent  of  some  centigrammes  for  every  5  grammes  we  have 
given.  The  urine  rapidly  takes  on  a  brownish-black  coloration, 
different  from  that  of  carbolic  acid,  which  is  tinted  black,  and 
from  creasote,  which  is  of  a  greenish  black. 

Acetic  acid,  in  small  quantity,  modifies  the  substance  which 
results  from  the  passage  of  naphthalin  into  the  urine.  Under 
its  influence  a  rosy  tint  appears,  which  acetic  acid  does  not  pro- 
duce in  normal  urine.  We  can  estimate  in  the  urine  a  body  of 
a  compound-sulphur  character,  resulting  from  the  combination 
of  naphthol  and  sulphur,  a  naphtho-sulphurous  acid,  which  may 
be  arranged  as  naphtho-sulphite  of  soda.  This  union  can  only 
have  occurred  by  sulphur  having  been  borrowed  from  the  organ- 
ism ;  that  is  to  say,  by  destroying  albumen  or  nitrogenous  matter. 
But  this  quantity  of  sulphur  is  insignificant,  as  I  have  been  able 
to  ascertain  by  the  aid  of  M.  Rosenstichl.  From  the  whole  of 


100  LECTURES   ON    AUTO-INTOXICATION. 

the  urine  passed  by  a  woman  who  had  taken  for  ten  days  5 
grammes  of  naphthalin  we  were  only  able  to  remove  0.03  centi- 
gramme of  naphtho-sulphite  of  soda  per  litre. 

For  ten  years  I  have  made  use  of  charcoal  in  large  doses, 
and,  thanks  to  it,  have  obtained  a  diminution  of  the  toxicity  of 
urine  and  of  fsecal  matter  without  preventing  fermentation. 
Since  then  I  have  added  iodoform  to  charcoal,  which  neutral- 
izes putrid  ferments,  according  to  the  formula :  Charcoal,  100 
grammes  ;  iodoform,  1  gramme. 

Following  Rossbach,  I  experimented  with  naphthalin  to 
solve  the  question  of  the  seat  of  the  infectious  agent  in  cholera; 
then  in  typhoid  fever,  gastric  fullness,  putrid  diarrhoeas ;  finally, 
in  the  healthy  individual,  without  injury  to  the  latter. 

I  give  the  formula :  Five  grammes  of  naphthalin,  mixed 
with  an  equal  quantity  of  sugar,  made  aromatic  with  1  or  2 
drops  of  bergamot,  divided  into  twenty  powders,  one  of  which 
is  to  be  taken  every  hour. 

Fsecal  matter  at  length  loses  its  odor,  unless  it  is  simply 
masked  by  that  of  naphthalin.  But  a  second  and  greater 
advantage  is,  that  fsecal  matter  loses,  to  a  great  extent,  its  tox- 
icity, the  putrefactions  within  the  intestinal  tube  being  com- 
pletely suppressed. 

In  the  case  of  a  man  the  subject  of  gastric  trouble,  35  to  40 
cubic  centimetres  of  urine  induced  death  for  every  kilogramme 
of  animal.  After  disinfection  of  the  faeces  by  naphthalin,  90  to 
100  cubic  centimetres  of  urine  were  harmless.  This  harmless- 
ness  of  the  urine  lasted  as  long  as  the  antisepsis  of  the  digestive 
canal.  Antisepsis  suppressed,  the  urine  became  toxic  again. 

With  charcoal  I  was  less  enlightened  upon  the  cause  of  the 
inoffeusiveness  of  the  urine,  since  it  fixed  the  coloring  matter 
of  the  biliary  secretion.  By  means  of  naphthalin  I  only  sup- 
press fermentation.  We  would  also  require  to  suppress  the 
bile ;  but  as,  in  the  case  of  people  in  whom  bile  ceases  to  flow 
into  the  intestine,  it  passes  into  the  blood,  the  problem  cannot  be 
solved.  We  would  require  to  have  an  individual  the  subject  of 
biliary  fistula,  and  suppress  in  him  alimentation.  All  causes  of 
toxicity  removed,  whatever  will  remain  of  a  toxic  character  in 
the  organism  would  be  attributable  to  the  poisons  of  disassimi- 
lation.  Here  is  research  for  the  future. 


INTESTINAL   ANTISEPSIS.  101 

To  sum  up  :  I  have  succeeded  in  demonstrating  that  not 
only  are  there  poisons  in  the  intestine,  but  that  the}'  are  a  con- 
stant menace  of  intoxication  to  the  organism.  After  having 
explained  the  sources  of  toxic  substances,  I  have  shown  their 
passage  through  the  organism,  their  elimination  by  the  urine, 
and  the  sewage-wave  ladened  with  toxicity  coming  from  other 
sources.  If  urine  is  not  formed,  there  may  result  from  this  fact 
intoxication,  which  will  often  be  of  intestinal  origin.  That  is 
why,  in  place  of  uraemia,  I  have  proposed  to  call  it  stercoraemia 
or  coprsemia. 

If  I  have  written  at  such  length  upon  plrysiological  data, 
it  is  because  they  were  indispensable  before  undertaking  the 
analysis  of  pathological  facts. 


LECTURE   XL 

PATHOGENESIS  OF  URJEMIA — DISTINCTION  BETWEEN  THE  SYMPTOMS 
OF  THE  PRE-UR.&MIC  PERIOD  OF  NEPHRITIS  AND  THE  SYMPTOMS 
OF  INTOXICATION. 

The  knowledge  of  the  action  of  the  toxic  substances  contained  in  the  urine  does 
not  explain  all  the  symptoms  of  nephritis.  It  only  explains  those  of  the 
period  of  intoxication,  when  the  organism  produces  more  poison  in  twenty- 
four  hours  than  the  kidneys  can  eliminate  in  the  same  time.  A  normal 
kidney  can  eliminate  more  toxic  material  than  it  does  in  an  ordinary  way. 

Examination  of  the  various  accidents  which  we  observe  in  diseases  of  the 

kidney  before  the  uraemic  period, — albuminuria,  cachexia  from  hypo-albu- 
minosis.  Dropsy.  Vascular  and  cardiac  troubles;  their  effect  upon  the 
digestive  canal  and  the  nutrition  of  the  skin.  Haemorrhages.  Eye  troubles. 
Spurious  serous  phlegmasias.  All  accidents  precipitated  may  come  on  when 

the  urine  is  still  normal  as  regards  quantity  and  density. When  the  renal 

impermeability  has  become  excessive,  the  period  of  intoxication  is  announced 
by  one  or  several  of  the  seven  poisons  which  normal  urine  contains,  variously 
associated.  There  would,  therefore,  be  not  one,  but  several  uraemias.  Clin- 
ical investigation  has,  for  some  time  past,  established  various  symptomatic 
forms,  and  the  five  theories  actually  in  existence,  which  are  proposed  in  order 
to  explain  the  pathogenesis  of  uraemia,  contain,  all  of  them,  an  element  of 
truth. 

WE  know  the  various  groups  of  toxic  substances  which,  in 
the  normal  state,  enter  into  the  blood  and  are  eliminated  by  the 
kidney.  By  lesions  of  the  kidney  allowing  of  the  accumulation 
of  toxic  products  in  the  organism,  it  is  apparent  that  we  can 
now  clearly  interpret  the  accidents  which  are  produced  in  people 
who  are  the  subjects  of  disease  of  the  kidney.  We  must  not 
delude  ourselves,  however;  the  pli3Tsiological  knowledge  which 
we  have  acquired  only  throws  light  upon  some  of  the  accidents 
which  complicate  diseases  of  the  kidnej^. 

Amongst  the  symptoms  of  nephritis,  many  do  not  belong  to 
the  domain  of  intoxication.  Besides,  every  disturbance  of  the 
renal  function  is  not  capable  of  determining  a  sufficient  accumu- 
lation of  toxic  substances  in  the  econonry,  and  for  sj'inptoms  to 
show  it.  In  order  that  intoxication  may  be  invoked,  it  is  not 
sufficient  that  the  kidney  should  be  diseased.  It  is  necessary 
that  its  permeability  should  be  diminished  to  a  degree  such  that 
(102) 


PATHOGENESIS   OP  UREMIA.  103 

it  can  no  longer  eliminate,  in  twenty-four  hours,  the  quantity  of 
poison  which  the  organism  forms  in  twenty-four  hours.  Now, 
it  is  certain  that  the  kidney  can,  in  the  normal  state,  eliminate 
infinitely  more  toxic  material  than  it  generally  does.  Let  us 
consider  what  a  normal  kidney  can  do.  Instead  of  the  1200  to 
1500  grammes  of  urine  which  it  secretes  ordinarily  in  twenty- 
four  hours,  a  normal  kidney  can  secrete  as  much  as  25  litres  of 
urine,  and  more.  Instead  of  20  to  30  grammes,  it  can  eliminate 
120  grammes  of  urea,  and  more,  as  in  a  large  number  of  cases 
of  diabetes  insipidus.  Instead  of  55  centigrammes  of  uric 
acid,  which  the  kidney  eliminates  in  the  normal  state,  it  can,  in 
cirrhosis  and  in  leukaemia,  eliminate  8  grammes  of  it,  and  more, 
in  twenty-four  hours.  It  can,  in  addition,  eliminate  other  ab- 
normal substances,  up  to  140  grammes  of  sugar  per  litre.  Add 
to  this  the  fat  existing  in  the  form  of  granules,  and  not  dis- 
solved (chyluria).  The  kidney  also  eliminates  substances  which 
it  ought  to  retain, — peptones  and  albumen. 

It  requires  the  kidney  to  be  considerably  diseased,  for,  owing 
to  its  permeability,  it  is  sufficient  alone  to  eliminate  the  poison 
formed  by  the  organism,  in  proportion  to  its  production.  Below 
this  rate  commences  intoxication  ;  but  before  this  arises  we  see 
abnormal  phenomena  appear,  and,  first  of  all,  albuminuria. 

Albuminuria  is  the  accident  of  bad  repute  in  diseases  of  the 
kidney, — that  to  which  we  attach  extreme  importance,  behind 
which  we  find  O3dema  and  all  the  rapidly  developed  or  slowly 
evolved  accidents  of  Bright's  disease,  and  which  we  regard  as 
causing  exhaustion.  Yet  it  is  often  a  few  centigrammes — at  the 
most,  a  few  grammes — of  albumen  which  the  patient  eliminates 
each  da}'.  Such  a  slight  spoliation  is  not  capable  of  causing  de- 
terioration of  the  system.  A  woman  who  is  nursing  loses,  with- 
out any  injury,  40  to  50  grammes  of  albumen  or  other  proteid 
matter  by  the  lacteal  secretion,  and  yet  the  system  is  not  weak- 
ened thereby.  Her  safeguard  is  the  integrity  of  her  appetite 
and  digestion.  She  loses  albuminoid  matter  under  one  form  and 
recuperates  it  under  another.  But,  in  the  same  way  as  in  the 
nurse,  insufficient  alimentation  and  vomiting  may  diminish  the 
proteids ;  and  if  the  renal  disease  is  accompanied  by  fever  or 
other  phenomena  which  prevent  nutrition  and  reparation,  intense 


104  LECTURES   ON   AUTO-INTOXICATION. 

albimiinuria  becomes  a  cause  of  exhaustion,  like  abundant  leucor- 
rhoea,  dysentery,  suppurations,  and  frequently-tapped  ascites. 
An  elimination  of  albumen  in  considerable  quantity  may  cause 
impoverishment  of  the  blood.  There  are  large  albuminurias, — 
from  8  to  12  grammes  in  twenty-four  hours.  This  last  limit  is 
seldom  exceeded  ;  we  mention  as  very  rare  that  of  16  grammes. 
I  have  seen  a  patient  lose  19  grammes  daily  of  albumen,  reck- 
oned as  dry  albumen  ;  it  was  in  a  case  of  amyloid  degeneration 
of  the  kidneys,  liver,  spleen,  and  stomach.  In  these  cases  we 
understand  that  a  rapid  cachexia  is  produced,  by  hypo-albumosis, 
when  the  nephritis  is  accompanied  by  functional  alterations  or 
lesions  of  the  digestive  canal. 

There  are  patients  in  whom  the  density  of  the  serum  falls 
from  1030  to  1013,  consequent  upon  the  absolute  want  in  the 
blood-plasma  of  proteid  matter,  and  of  a  relative  hydrsemia. 
There  is  produced  a  correlative  increase  of  water,  relative 
hydrsemia,  and,  besides,  often  enough,  an  absolute  hydrsemia, 
because  there  has  been  retention  of  water. 

The  extreme  cases  belong  chiefly  to  amyloid  nephritis,  be- 
cause in  such  the  liver,  spleen,  stomach,  and  intestine  are  dis- 
eased. All  the  organs  whose  function  it  is  to  transform  the 
peptones  of  digestion  into  serum-albumen  have  undergone  de- 
terioration at  the  same  time  as  the  kidney.  When  such  a 
large  number  of  organs  is  diseased  we  can  scarcely  regard 
all  the  accidents  which  happen  as  due  to  renal  impermea- 
bility. We  cannot  say  that  there  is  uraemia,  nor  even  kidney 
disease ;  there  is  a  general  disease  of  the  organs  concerned  in 
assimilation. 

Hydrsemia  is  not  always  caused  by  the  retention  of  water ; 
it  may  be  produced  by  diminution  in  the  amount  of  solid 
matter.  On  the  other  hand,  hydrsemia  may  be  prevented  by 
attacks  of  vomiting,  diarrhoea,  anasarca,  in  spite  of  oliguria; 
then  comes  thirst,  a  frequent  accident,  which  introduces  as 
much  water  as  the  accessory  emunctories  can  remove.  There  is 
then  a  collection  of  conditions  extremely  complex,  and  all 
foreign  to  intoxication ;  therefore  we  do  not  pretend  to  explain 
by  intoxication  most  of  the  accidents  of  nephritis. 

As  a  consequence  of  hypo-albumosis  there  appear  oedemas, 


•     PATHOGENESIS   OP    UREMIA.  105 

anasarca,  and  serous  accumulations  in  the  large  cavities.  Accord- 
ing to  Bartels,  the  hypothesis  of  Bright,  which  regards  hydrse- 
mia  as  favorable  to  the  diffusion  of  serum,  would  not  be  suffi- 
cient. Bartels  believes  that  there  is  a  hydrsemic  plethora.  He 
calls  to  his  aid  the  oliguria  which  generally  accompanies  oedema. 
And  yet  in  absolute  anuria,  such  as  is  produced  in  the  obstruc- 
tion of  the  two  ureters  by  calculi,  anasarca  is  exceptional.  I  do 
not  know  how  oedema  is  produced  in  albnminuria,  but  the 
hypothesis  of  Bartels  seems  to  me  to  be  inadmissible. 

In  a  goodly  number  of  cases  we  must  take  into  consideration 
both  vascular  and  cardiac  disturbance,  but  in  interstitial  nephri- 
tis, in  which  cardiac  lesion  is  the  rule,  we  find  little  oedema,  and 
in  amyloid  degeneration,  where  the  heart  is  normal,  dropsy  is 
extreme.  Yet  some  have  thought  that  the  hypertrophy  of  the 
heart  was  compensatory  to  the  renal  impermeability ;  at  any 
rate,  it  may  be  said  that  the  heart  is  a  dangerous  auxiliary, 
for  grave  accidents  may  result  from  this  so-called  providential 
lrypertroph}r. 

We  see  in  certain  cases  lesions  of  the  kidney,  heart,  and 
vessels  develop  simultaneously ;  all  the  vascular  system  is  seized, 
from  the  central  organ  of  the  circulation  up  to  the  finest  extrem- 
ities; and  if  the  kidney  can  suffer  from  such  a  delicate  symptom 
as  albuminuria,  we  have  no  right  to  disregard,  on  that  account, 
the  sufferings  of  other  organs.  We  know  bow  modifications  of 
the  cardio-vascular  S3rstem  bring  about  secretoiy  disturbance  in 
the  digestive  canal,  a  dryness  and  a  condition  of  prurigo  of  the 
skin,  which  may  be  the  consequence  of  a  nutritive  affection  of 
the  terminations  of  the  nerves  in  the  skin.  As  the  result  of 
vascular  lesions  we  also  observe  hemorrhages,  epistaxis,  htem- 
atemesis,  entorrhagias,  cerebral  haemorrhage,  and  purpura. 

All  this  is  not  allied  to  uraemia ;  it  is  all  beyond  intoxica- 
tion, and  shows  itself  when  the  urine  has  still  a  normal  density 
or  is  raised,  and  when  its  quantity  is  increased,  normal,  or 
slightly  diminished. 

All  the  foregoing  accidents  being  eliminated,  we  ask  what 
remains  to  cause  intoxication?  It  will  be  quite  legitimate  to 
attribute  to  it  one  part  only  of  the  phenomena  which  might 
supervene  when  the  impermeability  of  the  kidney  is  such  that 


106  LECTURES  ON   AUTO-INTOXICATION. 

it  can  no  longer  eliminate  the  toxic  substances  produced  by  the 
organism  in  proportion  to  their  formation. 

Testing  the  urinary  toxicity  would -give  us  sufficient  infor- 
mation on  this  point,  but  it  is  a  method  little  practiced,  and  at  the 
bedside  we  are  in  the  habit  of  making  estimations  upon  the  total 
quantity  of  urine  eliminated  in  twenty-four  hours  and  upon  its 
specific  gravity.  If  the  quantity  and  density  remain  normal  we 
have  the  right  to  say,  from  these  facts,  that  the  kidneys  func- 
tionate normallj7.  If  both  are  diminished,  there  is  a  danger  of 
intoxication. 

We  must  not,  in  this  estimation,  take  for  our  type  the  quan- 
tity of  urine  secreted  by  a  health)'  man  ;  a  sick  man  ingests 
and  destroys  little.  The  numbers — e.g.,  of  1350  cubic  centi- 
metres as  the  quantity  and  1019  as  the  density — are  too  high  for 
a  patient ;  they  are  only  normal  in  a  man  who  is  walking  about 
and  eating  well.  Lastly,  the  quantity  and  the  density  may 
balance  each  other  in  a  certain  measure. 

However  it  may  be,  all  the  accidents  of  nephritis  of  •which 
we  have  hitherto  spoken  are  produced  during  a  period  in  which 
the  urine  is  still  normal  in  quantity  and  density.  Retinitis,  amau- 
rosis,  inflammation  of  serous  membranes,  and  phlegmons  appear 
at  a  period  already  advanced.  And  yet  there  is  nothing  to  show 
that  the  retinites  are  uraemic  accidents  of  the  same  nature  as  the 
respiratory  disturbances,  or  coma  and  convulsions.  I  admit 
that,  in  individuals  who  retain  their  toxic  products,  all  the  cells 
of  the  organism  have  a  weakened  vitality,  only  bordering  upon 
inflammation  which  has  not  resolved.  But  these  incomplete 
phlegmasias,  cadema  of  glottis,  hnemorrhagic  and  purulent  peri- 
carditis, are,  at  any  rate,  only  accidents  further  removed  and 
indirectly  due  to  intoxication.  They  denote  simply  a  cachectic 
state,  of  which  poverty  of  blood  and  insufficient  alimentation 
are  the  principal  factors. 

Yet,  after  having  eliminated  from  the  category  of  uraemia 
all  these  symptoms,  all  the  accidents  that  we  have  just  reviewed, 
we  come  to  others  which,  in  the  advanced  periods  of  chronic 
nephritis  or  in  the  course  of  acute  nephritis,  directly  flow  from 
renal  imperfection  which  has  become  excessive.  Beyond  that 
we  enter  into  the  domain  of  intoxication. 


PATHOGENESIS  OF  URJEMIA.  107 

We  find  ourselves  in  the  presence  of  an  intoxication  which 
may  be  due  to  one  of  the  seven  poisons,  which  analysis  of  the 
products  of  toxicity  has  revealed  to  us,  or  to  several  amongst 
them,  associated  two  by  two,  three  by  three,  or  to  all  the  seven 
together ;  finally,  water  (the  elimination  of  which  may  be  pre- 
vented) may  play  a  part  in  the  morbid  accidents.  It  appears 
impossible  that  there  should  be  one  form  of  uraemia  only. 
Already  clinically  there  have  been  described  for  a  long  time 
different  symptomatic  forms.  Perhaps  there  is  a  place  in  patho- 
genesis  for  the  five  following  theories,  which  include  (1)  cere- 
bral oedema  (Traube) ;  (2)  urea  (Wilson) ;  (3)  ammonia 
(Frerich) ;  (4)  extractive  matters  (Schottin),  and,  notably, 
oxalic  acid  (Bence-Jones),  urochrome  (Thudicum),  and  (5) 
potass  (Feltz  and  Hitter). 


LECTURE  XII. 

PATHOGENESIS  OP  URAEMIA — DISCUSSION  OP  THE  EXCLUSIVE 
THEORIES. 

The  uraemic  period  of  nephritis  is  characterized  by  the  appearance  of  chronic 
or  paroxysmal  nervous  accidents, — cephalalgia,  dyspnoea  of  the  Cheyne- 
Stokes  type,  convulsions,  coma, — associated  or  not  with  disturbances  of 
calorification  and  with  other  symptoms  of  the  pre-uraemic  period;  for 

example,  cedemas. Clinical  observation  has  established  several  modes  of 

grouping  of  symptoms  of  the  uraemic  phase  whilst  seeking  to  relate  them  to 

certain    anatomo-pathological    forms. Every   inventor  of   a  pathogenic 

theory  has  appealed  to  bedside  observation  for  a  justification  of  his  opinion. 

Traube  incriminated,  as  the  cause  of  uraemic  accidents,  the  cerebral 

oedema  which  might  result  from  hydraemic  plethora.  His  opinion  is  awant- 
ing  in  anatomo-pathological  proofs,  and  rests  rather  upon  inadmissible 

physiological  arguments. Wilson  invoked  excess  of  urea  in  the  blood. 

Urea  cannot  explain  accidents  in  the  quantity  in  which  it  exists  in  the  blood 
of  uraemics.  Injection  of  urea  into  the  stomach,  into  the  cellular  tissue, 
into  the  veins  after  nephrectomy. 

I  HAVE  shown  that  many  of  the  accidents  called  ursemic 
happen  at  a  period  of  nephritis  in  which  the  retention  of  toxic 
products  is  inadmissible.  As  long  as  the  urine  is  of  sufficient 
quantity  and  has  a  density  high  enough,  there  is  no  intoxica- 
tion. The  question  of  uraemia  can  only  be  argued  from  acci- 
dents happening  at  a  time  beyond  that  in  which  imperfection  of 
the  kidney  has  become  excessive,  such  as  when  it  eliminates 
no  longer,  in  twent37-four  hours,  the  toxic  products  introduced 
into  the  organism  or  formed  by  it  during  this  length  of  time. 
Then  we  may  see  a  series  of  chronic  or  paroxysmal  nervous 
accidents  happen,  characterized  by  pain  in  the  head,  dyspnoea 
of  the  Cheyne-Stokes  type,  vomiting,  diarrhoea,  convulsions, 
and  coma,  at  the  same  time  as  a  certain  number  of  accidents  of 
the  preparatory  period  persist.  We  still  find  cedemas,  which 
increase  or  diminish ;  alterations  of  temperature ;  sometimes 
hypothermia,  which  may  fail  and  give  way  to  hyperthermia. 

The  nervous  accidents  may  be  isolated  or  associated  ;  and 
already,  from  this  point  of  view,  as  from  that  of  the  co-exist- 
ence of  unusual  symptoms,  the  presence  or  absence  of  low  tem- 
perature, cases  of  uraemia,  observed  clinically,  seem  so  different 
(108) 


DISCUSSION   OF   EXCLUSIVE   THEORIES.  109 

the  one  from  the  other  that  we  must  think  of  the  existence  of 
various  and  mixed  pathogenic  conditions.  Very  likely  we  have 
to  do  not  with  one  intoxication  only,  but  with  numerous  causes, 
which  may  be  isolated  or  associated ;  so  that  if  one  explanation 
holds  for  one  case  it  does  not  necessarily  hold  for  others,  and 
a  false  theory  in  one  case  may  not  be  so  in  others.  If  we  wish 
to  include  the  whole  pathogenic  study  of  uraemia,  we  must  be 
persuaded  that  we  cannot  offer  one  explanation  alone  of  all  the 
nervous  accidents  which  may  appear  in  the  course  of  disease  of  the 
kidne}r.  Besides,  clinical  observation  has  endeavored  to  group  a 
certain  number  of  particular  cases,  according  to  their  symptom- 
atic resemblances,  by  calling  to  its  aid  pathological  anatomy. 

There  exists  a  symptomatic  form,  characterized  by  early 
dropsy  of  the  anterior  surface,  developed  a  long  time  ago  or 
just  a  short  time  previously.  We  have  seen  oedema  increasing, 
the  urine  becoming  less  abundant,  its  density  increasing  (a 
greater  quantity  of  solid  matter  being  found  in  each  unit  by 
weight),  or  remaining  the  same.  The  patient  has  neither  diar- 
rhoea, vomiting,  nor  any  other  flux  capable  of  carrying  away 
water,  and  there  is  oliguria ;  there  is,  therefore,  retention  of 
water  in  the  organism.  The  other  normal  secretions  continue ; 
the  tongue  is  moist.  We  in  vain  seek  for  the  presence  of  ammo- 
nia in  the  expired  air.  In  these  cases  are  found  reunited  all  the 
conditions  of  hydraemia  or  of  hydraemic  plethora.  The  urine 
continuing  to  carry  away  the  total  quantity  of  solid  matter  which 
ought  to  be  eliminated  by  the  kidneys,  it  is  impossible  to  ex- 
plain, by  the  theory  of  intoxication,  the  accidents  which  arise. 
There  is,  on  the  contrary,  an  undoubted  accumulation  of  water 
in  the  organism.  Thus,  the  idea  has  arisen  that  the  accidents 
called  uraemic  are  due  to  an  accumulation  of  water. 

Traube  has  actually  thought  that  the  consequence  of  l^drae- 
mia  was  a  tendency  to  the  production  of  oedema,  and,  notably, 
to  cerebral  oedema.  Coindet  and  Odier  have  seen  there  suf- 
ficient conditions  to  explain  the  development  of  a  ventricular 
dropsy.  According  to  their  manner  of  viewing  the  subject, 
interstitial  oedema  or  ventricular  drops}7,  by  compressing  the  en- 
cephalon  within  and  without,  diminishes  the  space  left  free  for 
the  blood ;  hence  cerebral  anaemia  involving  the  production  of 


110  LECTURES   ON   AUTO-INTOXICATION. 

comatose  conditions  when  the  anaemia  is  especially  marked  at  the 
level  of  the  convolutions,  or  convulsions  if  it  predominate  in 
the  mesencephalon. 

If  we  wished  to  furnish,  like  Traube,  a  general  explanation 
of  the  facts  reputed  to  be  ursemic,  his  theory  would  be  false ;  and 
it  is  so  in  effect,  as  he  has  formulated  it.  Indeed,  in  the  large 
majority  of  cases  followed  up  by  an  autopsy  cerebral  oedema, 
ventricular  dropsy,  and  cerebral  anaemia  are  wanting.  And  not 
only  has  evaporation  not  demonstrated  the  existence  of  a  larger 
proportion  of  water  in  the  tissues  of  the  brain  than  normally, 
but  in  place  of  anaemia  it  is  easy  to  establish  congestion  pushed 
to  the  point  of  extreme  fullness  of  blood-vessels  and  to  ecchy- 
moses.  These  are  the  cases  that  disprove  his  theory.  But, 
besides,  this  must  hold  good  for  all  cases  or  its  falsity  is  not 
demonstrated ;  otherwise,  it  remains  a  pure  hypothesis  which 
does  not  rest  upon  any  foundation  of  direct  observation.  It  is 
untrue  even  as  a  theory,  for  a  certain  number  of  physiological 
arguments  invoked  by  Traube  are  inadmissible. 

In  a  large  number  of  cases  we  see  ursemic  accidents  produced 
in  patients  who  are  eliminating  water  in  excess ;  their  urine  is 
more  than  the  normal  in  quantity,  and  they  have  evacuations 
from  the  stomach  and  intestines. 

Hydraemia  should  have,  as  an  effect,  osdcma ;  but  it  would 
be  necessary  to  demonstrate  experimentally  this  relationship, 
for  neither  experimental  pathology  nor  clinical  observation 
confirms  it. 

Double  calculous  obstruction,  suddenly  developed,  produces 
uraemic  accidents,  at  the  end  of  a  recognized  time,  without 
inducing  oedema.  Thus  is  found  broken  one  of  the  links  in 
the  chain  of  reasoning  of  Traube. 

Richardson  has  injected  into  the  peritoneum  of  a  dog  a 
quantity  of  water  equivalent  to  one-fifth  of  the  weight  of  the 
animal.  He  has  produced  everj'thing  but  intoxication.  He 
has  caused  death  by  septicaemia,  rendering  possible,  thanks  to 
the  modifications  which  the  injection  had  suddenly  brought 
about  in  the  tissues,  the  escape  of  some  infectious  agent  from 
the  digestive  tube  or  from  without,  and  which  has  become 
capable  of  producing  septicaemia. 


DISCUSSION   OF   EXCLUSIVE   THEORIES.  Ill 

But,  in  what  disease  of  the  kidneys  do  we  flnd  in  the  body 
such  an  accumulation  of  water? 

Falck  has  injected  the  same  quantity  of  water  into  the  veins  ; 
he  has  seen  convulsive  accidents  and  death  ;  but  these,  we  might 
say,  from  the  point  of  view  of  experimental  pathology,  are  mon- 
strous operations  which  are  not  at  all  comparable  to  pathological 
facts.  It  is  the  exaggeration  of  a  legitimate  demonstration. 

We  may  inject  water  into  the  blood  in  considerable  quantity. 
Death  results  from  this  injection  when  we  have  introduced  into 
the  blood  122  grammes  of  water  per  kilogramme  of  animal,  in 
which  case  the  density  of  the  serum  of  the  blood  falls  to  1007  ; 
but  the  density  of  the  serum  of  the  blood  in  those  the  subjects 
of  uraemia  falls  seldom,  if  ever,  below  1016.  In  the  experiment 
of  Richardson  and  Falck  the  blood  is  nothing  more  than  a 
diluted  blood.  There  come  no  longer  into  the  capillaries  any- 
thing but  swollen  globules,  deprived  of  haemoglobin  and  inactive. 
How  can  we  compare  this  excessive  hy^lraemia  with  the  moderate 
retention  of  water  in  the  blood  which  may  exist  in  pathological 
cases  ?  In  absolute  anuria  uraemic  accidents  burst  forth  some- 
times before  the  fifty-sixth  hour,  when  a  man  has  not  as  yet  accu- 
mulated more  than  35  grammes  of  water  per  kilogramme  of  his 
weight.  But  we  know  that  injections  of  water  only  begin  to  be 
injurious  after  90  grammes  per  kilogramme. 

It  has  not  only  been  shown  that  the  viscera  may  be  invaded 
by  oedema.  Bartels  has  proved,  at  any  rate,  that  pulmonary 
oedema  does  not  exist  in  those  suffering  from  uraemia. 

Let  us  accept,  however,  if  you  please,  cerebral  oedema.  I 
am  ready  for  all.  concessions.  But  then  it  will  be  no  longer  a 
question  of  intoxication.  If  this  oedema  has  nothing  to  do  with 
the  retention  of  solid  matter  it  enters  into  the  category  of  the 
phenomena  which  we  have  previously  eliminated  from  the  list  of 
uraemia ;  they  are  part  of  the  mechanical  accidents  of  nephritis, 
and  are  improperly  included  amongst  chemical  accidents. 

But,  are  there  any  chemical  and  toxic  accidents  in  Bright's 
disease? 

We  can  furnish  proof—  j'es,  direct  proof — of  this.  Uraemic 
patients  are  those  whose  urine  has  lost  its  toxicity.  We  have 
seen  renal  elimination  diminish  in  quantity  and  the  density  of 


112  .  LECTURES  ON   AUTO-INTOXICATION. 

urine  fall,  and  we  have  been  forced  to  believe  that,  the  whole  of  the 
solid  substances  110  longer  being  eliminated,  the  individual  was 
going  to  become  intoxicated.  But  on  the  day  in  which  nervous 
accidents  called  ursemic  appear  the  urine  ceases  to  be  toxic. 
The  whole  of  the  urine  of  twenty-four  hours  from  a  ursemic 
patient  cannot  kill  a  rabbit,  nor  does  it  exceed  the  toxicity  of 
distilled  water.  And  yet,  whilst  with  120  cubic  centimetres  of 
distilled  water  per  kilogramme  of  animal,  used  as  an  intra-venous 
injection,  you  are  in  danger  of  inducing  death,  with  this  same 
dose  of  certain  urines  taken  from  ursemic  subjects  you  will  deter- 
mine no  phenomenon,  not  even  the  pupillary  contraction  caused 
by  normal  urine. 

There  yet  remains  to  be  known  what  is  or  what  are  the  poisons 
which  determine  the  toxic  and  chemical  accidents  of  ursemia.  Let 
us  return  for  a  moment  to  hypotheses.  In  the  first  line  is  placed 
the  old  hypothesis  of  Wilson,  which  has  recently  been  revived, 
and  according  to  which  the  accidents  called  ursemic  would  be 
caused  by  the  accumulation  of  urea  in  the  blood.  It  is  no  longer 
sufficient  to  say  that  the  urine  of  those  suffering  from  ursemia  con- 
tains less  urea.  It  has  been  shown  that  there  was  in  the  blood  as 
much  as  thirty-two  times  more  urea  than  in  the  normal  state ;  that 
in  the  muscles  there  was  as  much  as  1.20  grammes  instead  of 
simply  traces  of  it.  I  have  met  with  it,  amongst  those  suffer- 
ing from  choleraic  anuria,  in  the  tissues  where  it  is  not  formed 
normally.  The  theory,  therefore,  would  be  legitimate  save  for 
its  demonstration. 

Gallois  has  injected  into  the  stomach,  Treitz  into  the  veins, 
and  Richardson  into  the  cellular  tissue,  large  doses  of  urea. 
Grehant  and  Quinquaud  have  likewise  injected  it  into  the  cellu- 
lar tissue.  These  last  observers  have  seen  toxic  accidents. 
Treitz,  who  had  made  injections  into  the  veins,  has  not  observed 
anything.  Hammond  practices  nephrectomy  and  then  makes  an 
injection  of  urea, — the  animal  dies.  The  experiment  of  Ham- 
mond is  repeated  by  Frerichs,  Oppler,  and  Petroff,  and  these 
conclude  that  after  nephrectomy  the  animals,  into  which  they 
injected  urea,  do  not  die  more  quickly.  This  contradiction  was 
so  singular  that  Feltz  and  Hitter  have  repeated  the  experiment. 
They  have  at  length  induced  death  as  speedily  in  healthy 


DISCUSSION    OF   EXCLUSIVE   THEORIES.  113 

animals  as  in  those  upon  whom  they  had  performed  nephrec- 
tomy.  They  employed  urea  which  they  had  sent  from  Ger- 
many, so  as  to  have  it  purer.  The  verification  made,  it  con- 
tained sulphate  and  chloride  of  ammonia.  Hitter  began  to 
prepare  pure  urea  himself,  and,  setting  out  from  the  day  in 
which  he  made  injections  with  this  urea,  he  no  longer  deter- 
mined accidents.  Such  is,  perhaps,  the  explanation  of  the 
contradiction  between  various  experimenters. 

As  for  myself,  relying  upon  my  own  experiments,  I  say  that 
urea,  in  the  quantity  in  which  we  meet  with  it  in  the  organism, 
in  pathological  states,  cannot  be  invoked  to  explain  the  acci- 
dents called  ursemic. 

In  order  to  kill  a  man  it  would  require  the  quantity  of  urea 
which  he  makes  in  sixteen  days.  But,  in  double  calculous 
obstruction,  suddenly  developed,  uraemic  accidents  appear — 
sometimes  at  the  end  of  the  second  day  or  at  the  commence- 
ment of  the  third — at  the  time  that  man  has  not  yet  made  the 
eighth  part  of  that  amount  of  urea  which  is  necessary  in  order 
to  cause  death.  But  during  that  time,  as  we  know,  he  has  been 
able  to  accumulate  sufficient  of  other  toxic  substances  to  bring 
about  intoxication.  Clinical  observation  is  here,  therefore,  com- 
pletely in  accordance  with  experimentation  in  denying  to  urea 
the  power  of  producing  the  intoxication  called  uraemic. 


LECTURE  XIII. 

PATHOGENESIS  OF  URAEMIA — DISCUSSION  OP  THE  EXCLUSIVE 
THEORIES. 

Theory  of  ammoncemia  (Frerichs).  Is  the  carbonate  of  ammonia  resulting 
from  the  breaking  up  of  urea  in  the  blood  the  cause  ?  Is  urea  transformed 
into  carbonate  of  ammonia  in  the  digestive  canal  ?  (Bernard  and  Grandeau, 
Treitz,  Jaksch.)  Objection  to  the  theory  of  ammonsemia  as  the  absolute 

explanation  of  ursemic  accidents. Theory  which  incriminates  extractive 

substances;  that  of  Schottin,  Scherer,  Oppler,  Chalvet.  Creatincemia  of 
Jaccoud.  Examination  of  the  possible  action  of  each  of  the  extractive  sub- 
stances,— uric  acid,  hippuric  acid,  creatin,  creatinin,  leucin,  tyrosin,  taurin, 
xanthin,  hypoxanthin,  guanin.  Theory  which  invokes  the  coloring  sub- 
stance, urochrome  (Thudicum).  Element  of  truth  which  it  contains. 

THE  clinical  fact  of  which  we  are  going  to  seek  the  explana- 
tion is  this :  The  co-existence  of  nervous  disturbances,  called 
ursemic,  with  a  diminution  of  the  solid  matter  contained  in  the 
urine  of  twent}r-four  hours, — a  diminution  proved  by  the  volu- 
metric examination  of  the  whole  of  the  urine  of  twenty-four 
hours  and  the  examination  of  its  densit3r. 

I  have  shown  that  this  diminution  of  solid  matter  of  the 
urine  had  for  its  corollary  the  retention  of  toxic  material,  since 
I  have  proved  the  harmlessness  of  the  urine  passed  by  uraemic 
subjects. 

After  this,  whilst  reviewing  the  various  hypotheses  which 
have  been  built  upon  the  nature  of  the  poison  or  poisons,  the 
retention  of  which  produces  uraemic  accidents,  I  have  combated 
the  theory  which  recognizes  this  poison  in  urea;  not  that  I  deny 
the  toxicity  of  urea  (I  admit  that  of  distilled  water),  but  because 
I  am  certain  that  urea  cannot  be  toxic  in  the  dose  in  which  it 
exists  in  the  blood  of  unemic  patients. 

Urea  being  thus  dethroned,  we  can  conceive  how,  incapable 
as  it  is  of  causing  injury  by  itself,  it  may  become  harmful  after 
having  undergone  transformation.  Frerichs  has  advanced  the 
theory  that  the  carbonate  of  ammonia  resulting  from  the  disinte- 
gration of  urea  is  the  pathogenetic  poison  of  uraemia ;  such  is  the 
(114) 


UREMIA    NOT   DUE   TO   AMMONIA.  115 

theory  of  ammonsemia.  As  was  said  when  discussing  oedema, 
some  have  twisted  the  clinical  aspect,  in  order  to  give  a  symptom- 
atic entirety  which  would  appear  to  be  in  accordance  with  theory. 
It  has  been  said  that  a  particular  form  of  uraemia  shows  itself 
in  those  suffering  from  albnminuria  without  oedema,  but  having 
diarrhoea  and  vomiting  and  with  dry  tongue.  Then  supervene 
severe  eclamptic  accidents.  The  urine  is  scanty,  and  of  little 
density.  Some  may  have  found  ammonia  in  the  blood,  and 
the  ammoniacal  exhalation  of  the  breath  has  been  sometimes 
established.  Here,  then,  is  a  theory  which  stands  well  simply 
as  a  theor}'.  Yet  let  us  see,  for  a  little,  some  of  the  details. 
One  thing  alone  is  convincing  in  this  picture, — the  diminution 
in  the  quantity  and  densit}'  of  the  urine.  But  the  retention  of 
ammonia  is  insufficient  to  explain  this  diminution  of  the  density. 
The  presence  of  ammonia  in  the  urine,  although  it  is  denied 
still  by  many  authors,  is  really  and  simply  a  trace, — especially 
at  certain  hours  of  the  day.  When  I  was  physician  at  the 
Bicetre,  eight  years  ago,  I  established  the  presence  of  ammonia 
in  the  urine  after  meals  composed  of  roasted  meat, — that  is, 
alimentary  ammonia ;  otherwise,  these  ammonurias  consequent 
upon  meals  are  feeble. 

The  presence  of  ammonia  in  the  expired  air  belongs  to  a 
large  number  of  pathological  and  even  normal  cases  ;  it  is  suf- 
ficient that  there  may  have  been  diyness  of  the  throat  and  of 
the  mouth,  owing  to  diminution  of  the  secretions. 

We  have  met  with  ammonia  in  the  blood  of  some  who  were 
the  subjects  of  uraemia,  but  normal^  we  find  traces  of  it  in  the 
blood  ;  there  is  constantly  some  of  it  in  the  blood  of  cadavera. 
There  is  nothing,  therefore,  to  authorize  the  incrimination  of  the 
transformation  of  urea  into  carbonate  of  ammonia.  Besides,  if 
urea  is  transformed  into  carbonate  of  ammonia,  it  is  not  by  the 
phenomenon  of  retention, — it  is  by  a  fact  of  faulty  nutrition. 

But  if  nothing  authorize  the  admission  of  this  transforma- 
tion as  the  cause  of  unemia,  here  is  what  authorizes  its  rejec- 
tion. When  we  inject  urea  into  the  blood,  it  is  eliminated  in  its 
entirety  in  twenty-four  hours,  without  the  ammonia  of  the  urine 
being  increased  (Feltz  and  Ritter).  The  amount  of  urea  found 
in  the  urine  exceeds  but  slightly  that  of  the  injected  urea ; 


116  LECTURES  ON   AUTO-INTOXICATION. 

besides,  normal  urea,  owing  to  its  diuretic  action  and  by  its 
bathing  the  tissues  better,  leads  to  the  elimination  of  an  excess  of 
urea;  but  we  do  not  find  ammonia  in  the  urine,  or  not  more  than 
in  the  normal  state.  Therefore,  the  theory  of  Frerichs  is  wrong. 

Bernard  and  Grandeau,  Treitz,  and  Jaksch  have  thought  that 
urea  may  be  transformed  into  carbonate  of  ammonia,  not  in  the 
blood,  but  in  the  digestive  canal,  after  having  passed  through 
the  intestinal  wall.  But  the  renal  path  is  the  natural  channel 
of  elimination,  and  so  elective  is  it  for  urea  that  it  is  all  but 
impossible  that  it  should  take  any  other.  Urea  is  eliminated  fifty 
times  more  quickly  by  the  kidney  than  by  any  other  emunctory. 
If  1  kilogramme  of  blood  contains  16  centigrammes  of  urea,  1 
kilogramme  of  urine  contains  16  grammes.  But  it  is  the  plasma 
of  the  blood  which  delivers  the  urea,  and  1  kilogramme  of  plasma 
contains  32  centigrammes  of  urea, — fifty  times  less  than  the  urine 
contains.  Urea,  as  I  have  said,  passes  through  the  kidney  in 
the  ratio  of  52,  while  water  is  as  1.  As  regards  the  other  organs 
of  elimination,  on  the  contrary, — through  the  wall  of  the 
stomach,  for  example, — the  filtration  of  urea  is  just  the  same  as 
for  water.  The  liquid  secretion  contains  urea  and  water  in  the 
same  proportion  as  the  plasma  of  blood. 

Blood  cannot,  therefore,  carry  to  the  stomach  and  intestine 
sufficient  urea  for  its  transformation  to  explain  intoxication. 
In  1872  and  1873  I  have  shown  this  fact,  apropos  of  hysterical 
vomiting,  attributed  wrongly  to  ischuria  or  anuria. 

As  for  invoking  the  disintegration  of  urea,  in  order  to 
explain  the  presence  of  ammonia  in  the  digestive  canal,  it  is 
quite  useless.  There  is  enough  of  it  normally,  without  the  inter- 
vention of  urea.  Can  we  say  that  ammonia  may  not  play  some 
other  part  in  uraeinic  accidents  ?  I  only  say  that  ammonaemia  is 
not  an  explanation  applicable  to  the  whole  of  the  facts  of 
uraemia,  and  that  neither  in  the  intestine  nor  in  the  blood  can 
urea  produce  ammonia  in  sufficient  quantity  to  bring  about 
intoxication. 

Nevertheless,  ammonaemia  may  be  produced  in  cases  of  abso- 
lute retention  by  the  kidney.  Ammonia  is  toxic,  in  moderate 
doses,  like  potass ;  it  produces  convulsions  and  a  great  fall  of 
temperature.  This  symptom,  which  ammoniacal  intoxication 


UR2EMIA   AND   THE   PRESENCE   OF   EXTRACTIVES.  117 

produces  in  the  highest  degree,  is  only  an  accident  contingent 
to  certain  uraemias.  It  may  be,  therefore,  that  ammonia  belongs 
to  the  number  of  toxic  substances  the  accumulation  of  which 
in  the  economy  causes  accidents,  but  it  is  not  demonstrated  that 
the  uraemic  accident  can  be  explained  by  the  presence  of  am- 
monia in  the  blood.  We  reject  ammonaemia  as  the  absolute 
explanation,  whilst  admitting  that  it  may  be  the  key  to  certain 
peculiarities,  to  some  of  the  special  symptoms  of  uraemia,  and 
that  it  may  particularly  arise  in  cases  where  intestinal  fermenta- 
tion is  increased.  Hypothermia  is  produced  by  normal  urine, 
but  this,  once  it  is  filtered  through  charcoal,  loses  this  property. 
Urinary  ammonia  passes  through  the  filter  whilst  the  substance 
which  determines  hypothermia  is  fixed  on  the  charcoal.  The 
hypothermia  of  certain  uraemias  is  not,  therefore,  capable  of 
being  attributed  to  ammonia. 

There  exists  in  urine  a  group  of  bodies  which  are  not  all 
named,  and  which  are  confounded  under  the  title  of  extractive 
substances.  By  degrees  we  recognize  the  chemical  characters  of 
some  of  them, — so  much  so  that  the  unknown  part  of  the 
extract  becomes  gradually  less  and  less.  For  a  long  time,  now, 
have  these  extractive  substances  been  incriminated  by  Scherer, 
Schottin,  Oppler,  Perls,  and  Chalvet.  In  this  way  has  the 
theory  of  poisoning  by  extractive  substances  originated  which 
Jaccoud  has  formulated,  under  the  name  of  creatinaemia,  with- 
out accusing  more  particularly  creatin,  except  in  symbolizing, 
under  this  category,  the  toxic  action  of  all  the  group. 

Clinical  observation,  which  has  pretended  to  give  support  to 
the  different  theories,  brings  to  this  its  array  of -observations; 
but,  if  we  examine  the  facts  cited  as  bearing  upon  poisoning  by 
extractive  substances, — for  example,  those  of  Chalvet,  who  has 
demonstrated  in  these  cases  the  increase  of  extractive  matters 
in  the  blood, — we  do  not  see  such  or  such  a  clinical  symptom 
predominate.  It  is  the  picture  of  uraemia  complete  in  all  its 
forms,  with  the  exception  of  this  form  of  supposed  uraemia  in 
which  the  urine  contains  in  twenty-four  hours  a  quantity  of 
solids  equal  or  superior  to  the  normal. 

In  the  cases  in  which  Chalvet  and  those  who  share  his 
opinion  have  spoken,  we  see  the  amount  of  the  extractives,  of 


118  LECTURES  ON   AUTO-INTOXICATION. 

urea,  and  coloring  matter  diminish  in  the  urine  ;  in  the  blood 
extractives  increase  whilst  the  toxicity  of  the  urine  diminishes, 
as  I  have  shown.  That  is  true  uraemia.  .Well,  let  us  see  what  may 
be,  from  the  point  of  view  of  the  production  of  toxic  accidents, 
the  action  of  each  of  the  organic  substances  taken  from  this 
group  of  extractives  : — 

Uric  acid  is  not  toxic  in  the  dose  of  0.64  gramme  per  kilo- 
gramme of  the  animal.  Hippuric  acid,  according  to  Challon, 
Feltz,  and  Hitter,  can  only  become  toxic  in  the  quantities  formed 
by  the  animal  in  ten  to  twelve  days.  I  have  injected  into  the 
veins  of  the  rabbit  hippuric  acid,  dissolved  in  water  by  the  help 
of  a  little  soda,  in  the  dose  of  4.59  grammes  per  kilogramme  of 
animal,  without  inducing  the  slightest  toxic  phenomena.  This 
inoffensive  amount  represents  nearly  the  whole  quantity  which  the 
animal  would  have  required  one  hundred  days  to  make.  Creatin 
undoubtedly  increases  in  the  blood  of  individuals  who  succumb 
to  uraemia  (Scherer,  Schottin,  Hoppe,  Oppler).  Is  the  toxicity 
due  to  it?  Challan  finds  it  toxic,  Testut  not  toxic.  Feltz  and 
Ritter  have  not  been  able  to  kill  an  animal  by  injecting  into  it  all 
at  once  the  quantity  of  creatin  which  it  excretes  in  seventeen 
days.  Creatin  may,  therefore, be  incriminated  still  less  than  urea  ; 
for,  if  urea  can  kill  when  it  is  injected  abruptly  into  the  veins  of 
an  animal  in  the  quantity  which  it  would  have  formed  in  sixteen 
days,  we  do  not  determine  in  it,  according  to  my  experience,  any 
appreciable  toxic  accident,  by  injecting  into  it  the  quantity  of 
creatin  which  it  would  have  formed  in  seventy-two  days.  Crea- 
tinin,  which  exists  in  the  blood  in  such  small  quantity  that  it 
appears  doubtful  to  many  physiologists,  is  formed  in  the  kidney 
by  transformation  of  creatin.  Could  it  be  taken  up  again  by 
the  blood,  in  case  of  obstruction  to  the  renal  excretion  ?  Feltz 
and  Ritter  have  proved  that  the  creatinin  excreted  in  six  days 
does  not  kill,  but  that  death  may  be  caused  by  the  quantity 
which  is  excreted  in  thirteen  days.  It  can,  therefore,  induce 
intoxication,  if  it  exist  in  the  blood  in  sufficient  quantity.  But 
it  is  an  energetic  base,  capable  of  producing  accidents  by  virtue 
of  its  excess  of  alkalinity.  It  can  only  be  employed  in  the 
form  of  salts.  The  chloride  of  creatinin  is  hardly  injurious  ; 
the  quantity  of  creatinin  excreted  during  ten  days,  and  injected, 


UREMIA   AND   THE   TOXICITY   OP   COLORING   SUBSTANCES.         119 

in  the  form  of  crcatinin  chloride,  by  .111  intra-venous  channel, 
does  not  hasten  death  by  one  minute,  in  the  case  of  a  dog,  after 
nephrectoiny.  Death  has  been  induced  on  the  third  day,  as 
ordinarily  (Feltz  and  Hitter). 

Leucin:  All  that  water  can  dissolve  of  it  produces  no  acci- 
dent (Feltz  and  Hitter).  The  quantity  of  tyrosin  excreted  in 
three  days  by  sick  men  is  not  followed  by  any  toxic  effect. 
Taurin,  in  the  dose  of  0.5  gramme  per  kilogramme  of  animal,  is 
without  effect.  Xanthin,  hypoxanthin,  and  guanin  do  not  pro- 
duce any  result  either. 

The  coloring  substances  have  been  incriminated  ~by  Thudi- 
cum,  on  account  of  the  feeble  coloration  of  the  urine  of  those 
suffering  from  uraemia.  We  have  seen  already  that  normal 
urine  loses  the  one-half  of  its  toxicity  by  decoloration  ;  decolor- 
ized bile  is  also  less  toxic.  The  coloring  matters  are,  therefore, 
suspected  by  me  from  their  toxicity  point  of  view ;  but  does  not 
filtration  by  charcoal  remove  from  the  urine  any  other  thing 
than  the  coloring  substances  ?  I  am  not  right  in  saying  that  the 
coloring  substances  are  the  true — the  principal — cause  of  the 
toxicity  of  urine.  Nevertheless,  they  belong  to  the  group  of 
those  organic  substances  to  which  we  ought  to  attribute  nearly 
the  one-half  of  this  toxicity.  I  have  tried  to  estimate  the 
degree  of  toxicity  of  one  of  the  coloring  substances  of  the 
urine,  viz.,  nrobiliu.  Thrice  I  have  made,  in  the  case  of  a 
rabbit,  an  intra-venous  injection  of  this  substance ;  thrice  the 
experiment  has  failed,  from  want  of  sufficient  quantity  of  ma- 
terial. I  can  only  say  that,  if  bilirubin  kills,  after  a  dose  of  5 
centigrammes  per  kilogramme,  urobilin,  in  a  dose  of  15  centi- 
grammes, does  not  kill  at  all. 


LECTURE  XIV. 

PATHOGENESIS   OP   URAEMIA — THE    PART    PLAYED  BY   ORGANIC 
SUBSTANCES  AND  MINERAL  MATTERS  IN  UR^EMIC  INTOXICATION. 

Urea  represents  one-seventh  or  one-eighth  of  the  total  toxicity  of  urine  ;  ammo- 
nia contributes  to  it  a  part  scarcely  appreciable.  We  can  accord  to  the 
coloring  substances,  and  others  fixeil  by  charcoal,  two-fifths  of  the  toxicity ; 
but  the  sum  of  all  the  organic  matter  represents  only  two-thirds  of  the  total 

toxicity.     The  .difference  is,  therefore,  made  up  by  the  mineral  matters. 

Exaggerated  statements  of  Feltz  and  Ritter,  who  consider  them  the  sole 

cause  of  uraemia. -Analysis  of  the  action  of  various  mineral  matters. 

Earthy  salts ;  alkaline  salts.  Small  importance  of  the  salts  of  soda.  Im- 
portance of  the  salts  of  potass  (chloride  of  potassium ;  phosphate,  sul- 
phate, and  phenylsulphate  of  potass). Physiological  antagonism  between 

narcotizing  substances  and  those  of  an  organic  and  mineral  nature,  which 
cause  convulsions.  The  predominance  of  coma  or  convulsions  in  uraemia 
depends  upon  the  retention  of  convulsion-causing  or  narcotizing  substances. 
Uraemia  is  a  mixed  form  of  poisoning,  and  due  to  many  causes. 

IN  recapitulating  the  bodies  in  which  we  recognize  a  certain 
toxic  power,  we  find  urea,  which  would  represent  one-seventh  or 
one-eighth  of  the  total  toxicity  of  urine;  ammonia,  which  is 
toxic,  but  in  a  fraction  which  escapes  us  ;  those  substances  which 
behave  in  the  manner  of  coloring  matters,  being,  like  them,  fixed 
by  charcoal,  and  to  which  we  ascribe  two-fifths  of  the  toxicity. 
Each  one  of  these  bodies  induces  intoxication,  and  may  play  its 
own  part ;  but  the  sum  of  all  these  organic  substances  only  rep- 
resents two-thirds  of  the  whole  toxicity  of  the  urine.  What 
is,  then,  the  difference  necessary  to  complete  this  totality  ?  There 
remains  to  us  the  mineral  substances  which,  according  to  Feltz 
and  Ritter,  would  be  the  exclusive  cause  of  the  toxicity.  There 
is  evidently  fallacy  in  the  statement  of  these  authors,  who 
have  made  such  remarkable  researches.  They  refuse  to  take  any 
notice  of  partial  or  fragmentary  intoxications  ;  they  do  not  wish 
to  admit  as  a  toxic  agent  anything  but  one  substance  alone. 
This  is  the  vulnerable  point  of  their  work. 

These  experimenters,  who  deny  that  all  the  toxic  action  is  due 
to  the  organic  substances,  have  yet  recognized  their  toxicity  ;  but 
they  do  not  take  any  account  of  these  organic  substances,  because 
(120) 


UREMIA    AND   MINERAL   SUBSTANCES.  121 

l>y  them  alone  they  have  not  been  able  to  produce  death,  not 
having  carried  the  injection  sufficiently  far,  and  in  strong-enough 
doses.  In  the  case  of  an  animal  dying  within  three  days  after 
nephrectomy,  they  have  said  that  the  cause  of  death  could  only 
be  the  substance  which  kills  in  a  quantity  equal  to  that  which  is 
normally  excreted  in  three  days.  Now,  since  by  the  extract  of  the 
organic  substances  of  the  urine  of  three  days  the}r  have  not  been 
able  to  produce  death,  they  deny  to  the  organic  substances  every 
toxic  action,  without  wishing  to  admit  that  their  partial  toxicity 
could  be  regarded  as  an  explanation  of  the  complete  toxicity. 

Let  us  see,  however,  with  MM.  Feltz  and  Hitter,  what  the 
mineral  substances  can  do  ?  These  are  vei\y  numerous,  but  a  large 
number  of  them  can  be  left  out  of  consideration,  on  account  of 
their  insignificant  weight.  A  man  of  75  kilogrammes  eliminates 
in  twenty-four  hours  1350  grammes  of  urine,  the  densit}'  of  which 
is  1019.  This  urine  contains  59  grammes  of  solid  matter,  which 
is  decomposed  into  43  grammes  of  organic  matter  and  16 
grammes  of  mineral.  These  last  are  composed  of  2  grammes  of 
earthy  salts  (salts  of  lime  and  magnesia),  4  grammes  of  salts  of 
potass,  and  10  grammes  of  salts  of  soda,  including  in  these 
weights  the  acids  of  the  bases.  If  we  state  these  as  being  the 
figures  for  the  composition  of  a  litre  of  urine,  we  have  : — 

finlkl  mittpr  44  PTimTnps  S  Organic,  32  grammes.  (  Earthy  salts,      1.50  grammes, 
lid  matter, «  grammes,  j  Mineral)  12  grailimes.  )  Salts  of  potass,  3.00  grammes. 

(  Salts  of  soda,    7.50  grammes. 

The  whole  of  the  earthy  salts  do  not  come  out  well  in  experi- 
ment, on  account  of  the  difficulty  which  there  is  in  maintaining 
them  dissolved  in  the  blood-plasma  by  intra-venous  injection.  I 
cannot,  therefore,  say  anything  about  them.  Besides,  they  are 
in  small  quantity  in  the  mineral  mass.  The  alkaline  salts,  on 
the  contrary,  are  verj'  soluble.  They  are  of  large  quantity,  and 
deserve  our  attention. 

The  salts  of  soda  seem  the  more  important  on  account  of 
their  weight.  In  reality  they  have  only  a  feeble  toxicit}-.  Chlo- 
ride of  sodium  kills  1  kilogramme  of  animal,  in  the  dose  of  5.17 
grammes;  but  chloride  of  sodium  is  the  most  toxic  of  the  salts 
of  soda  of  the  urine.  The  soda  of  the  urine  of  twent3'-fotir 
hours  would  kill,  at  the  outside,  2  kilogrammes,  whilst  this 
quantity  of  urine  kills  30. 


122  LECTURES   ON   AUTO-INTOXICATION. 

It  is  otherwise  with  the  salts  of  potass.  They  are  occa- 
sionally present  in  large  quantity, — 3  milligrammes  per  cubic 
centimetre  of  urine.  Forty  to  sixty  cubic  centimetres  of  urine 
being  toxic  (the  mean  45),  the  quantity  of  urine  which  kills  one 
kilogramme  of  animal  would  contain  nearly  13  or  14  centi- 
grammes of  salts  of  potass.  This  would  be  nearly  a  suffi- 
cient quantity  if  all  the  salts  of  potass  were  represented  by 
chloride  of  potassium ;  but  there  are  the  phosphate,  sulphate, 
and  phenylsulphate  of  potass,  which  do  not  have  the  same 
toxicit}^.  The  chloride  of  potassium  is  the  most  toxic  ;  it  kills 
in  the  proportion  of  18  centigrammes  per  kilogramme  of  animal. 
But  the  phosphate  of  potass  only  determines  toxic  accidents 
after  a  dose  of  26  centigrammes.  With  the  phenylsulphate  we 
have  seen  toxic  accidents,  but  not  death.  These  differences  of 
toxicity  explain  to  us  that  the  mixture  of  the  salts  of  potass 
gives  a  less  toxicity  than  the  chloride  of  potassium. 

Like  Feltz  and  Hitter,  I  have  destroyed  the  organic  matter 
of  urine  and  dissolved  the  mineral  substances,  and  I  have  noticed 
that  frequently,  contrary  to  their  statements,  the  salts  of  potass 
contained  in  50  cubic  centimetres  of  urine  do  not  induce  any 
accident,  but  that  accidents  arise  if  -we  take  the  salts  of  potass 
contained  in  a  double  quantity  of  urine.  In  order  to  kill,  there 
is  required  sometimes  a  qantity  of  potass  double  that  which  the 
usual  quantity  of  urine  causing  death  contains.  Besides,  this 
quantity  of  potass  kills  in  quite  another  way,  with  convulsions ; 
whilst  normal  urine,  taken  during  the  height  of  the  day,  does 
not  induce  convulsions.  In  death  by  potass  the  heart  is  arrested ; 
it  continues  to  beat,  however,  when  it  is  urine  which  has  caused 
the  poisoning.  A  normal,  decolorized  urine  which  still  contains 
nearly  all  its  potass  does  not  kill,  even  when  we  increase  the  dose 
by  one-half,  and  then  it  kills  without  convulsions ;  in  spite  of 
the  larger  dose,  the  action  of  potass  remains  obscured. 

We  have  already  spoken  of  these  toxic  associations  which 
exist  in  urine.  The  convulsive  substance  insoluble  in  alcohol, 
when  added  to  that  which  is  soluble  in  alcohol,  does  not  give 
rise  to  convulsions.  It  is  the  result  of  a  physiological  antago- 
nism. A  substance  which  determines  convulsions  is  neutralized 
by  another  organic  substance  which  produces  narcosis,  and  this 


INFLUENCE   OF   POTASS.  123 

association  of  the  two  hinders  the  appearance  of  convulsions. 
There  is  an  antagonism  between  the  narcotic  substances  soluble 
in  alcohol  and  the  convulsive  substances  which  are  insoluble; 
a  possible  antagonism,  too,  between  the  first  and  potass.  The 
equilibrium  resulting  from  the  antagonism  between  these  various 
substances  may  be  broken  by  increasing  either  the  potass  or  the 
convulsive  organic  substance.  There  are  pathological  urines 
which,  though  decolorized,  retain  their  convulsive  power;  this 
is  perhaps  due  to  the  potass.  Convulsive  urines  are  especially 
febrile  urines,  since  there  is  suppression  of  alimentation  and  an 
increase  of  cellular  destruction. 

The  diminution  of  alimentation  does  not  introduce  more 
potass  into  the  economy  ;  it  diminishes  the  totality  of  the  min- 
eral salts.  But  the  increase  of  disassimilation  augments  certain 
nitrogenous  substances,  and  particularly  potass,  by  destroying 
the  mineral  frame-work  of  the  cells.  Also,  whereas  potass  only 
represents  one-fourth  of  the  whole  mass  of  the  mineral  sub- 
stances, we  find  potass  present  in  quantity  at  least  equal  to  the 
soda.  If  urine  become  scant}7,  if,  instead  of  1000  grammes, 
the  secretion  falls  to  500,  admitting  the  specific  gravity  to  be 
equal  or  higher  even  than  the  normal,  the  quantity  of  mineral 
matter  which  it  carries  away  may  be  equal  to  the  normal,  per 
litre,  but  not  for  the  twenty-four  hours ;  the  emunction  falls  to 
one-half  or  two-thirds  of  that  which  it  ought  to  be ;  there  is 
produced  in  the  organism  an  accumulation  of  mineral  substances, 
particularly  potass.  This  may  then  become  a  cause  of  intoxica- 
tion ;  for  the  substances  which  are  antagonistic  to  it  in  the  nor- 
mal state  no  longer  suffice  to  neutralize  its  convulsive  action. 
We  know  that,  amongst  ursemic  phenomena,  there  may  be,  in 
certain  conditions,  a  predominance  of  the  action  of  potass,  which 
may  represent  two-thirds  of  the  toxicitj7,  instead  of  one-third. 

The  study  of  the  accidents  which  arise  from  intoxication  by 
potass  leads  up  to  the  denial  to  it  of  the  role  of  its  being  the  sole 
cause  of  uraemia.  There  are  summed  up  in  this  word  convul- 
sions and  death  in  opisthotonos ;  but  we  observe  neither  con- 
traction of  the  pupil,  diuresis,  low  temperature  due  to  dimin- 
ished calorification,  nor  salivation.  All  the  salts  of  potass  kill 
with  stoppage  of  the  heart,  which  urine  does  not. 


124 


LECTURES  ON   AUTOINTOXICATION. 


Thus  I  admit  that  potass  is  toxic,  but  not  that  urines  are 
rendered  toxic  by  it  alone.  If  we  seek  in  clinical  facts  some 
reasons  for  or  against  the  exclusive  pathogenic  role  of  potass, 
we  find  in  uraemia  reasons  to  reject  the  affirmation.  First,  we 
must  show  that  in  those  suffering  from  uraemia  there  is  an  accu- 
mulation of  potass ;  but  observers  who  have  believed  that  they 
have  found  this  in  excess  have  estimated  their  dosage  upon  the 
total  quantity  of  blood.  Now,  what  is  toxic  in  the  blood  can 
only  be  what  is  in  solution  in  the  plasma;  what  is  held  as  a 
constituent  part  of  the  living  cell  by  force  of  tension  cannot 
take  any  part  in  toxic  actions.  There  is  in  serum  only  traces 
of  potass.  In  the  researches,  otherwise  insignificant  and  con- 
tradictory, which  have  been  made  upon  the  variations  of  potass, 
we  have  taken  notice  of  the  serum  and  of  the  globules,  which 
are  so  richly  provided  with  it  and  so  strong  in  their  affinity  for 
it.  Suppose  even  that  there  is  an  accumulation  of  potass  in  the 
blood-plasma ;  it  would  not  explain  the  unemia,  in  which  there 
are  only  convulsions ;  it  would  not  explain  the  subjective  symp- 
toms which  precede  those  or  accompany  them, — narcosis ;  ursemic 
coma;  pupillary  contraction,  which  is  a  prominent  phenomenon 
in  uraemia  (a  circumstance  impressed  upon  me  during  the  course 
of  the  last  cholera  epidemic).  All  these  symptoms  intoxication 
by  the  whole  of  the  substances  of  the  urine  explains,  but  not 
by  potass.  We  can  appreciate  the  relative  toxicitj"  of  the  prin- 
cipal mineral  substances  of  the  urine  from  the  following  table, 
which  I  have  taken  from  experiments  made  in  common  with  M. 
Tapret :— 


NAME  OF  SUBSTANCE. 

Index  of 
Solution. 

Quantity  of  Substance 
Necessary  to  Kill  One 
Kilogramme  of  Animal. 

Chloride  of  potassium, 

Sulphate  of  potass,     .     .          .     . 

Phosphate  of  potass,  ...          .    . 

0.263  gramme 

Chloride  of  sodium  

ttV 

Sulphate  of  soda,   
Phosphate  of  soda,     

? 

9.00    grammes. 

Chloride  of  magnesium,      .... 

? 

Sulphate  of  magnesia 

Chloride  of  calcium,  . 

,     •        gramme. 

' 

ORGANIC   SUBSTANCES   AND   MINERAL    MATTERS.  125 

If  we  apply  these  facts  to  the  results  of  the  analyses  of  urine 
of  man,  we  arrive,  by  means  of  calculations,  of  which  I  shall 
spare  you  the  details,  at  the  following  results  : — 

One  kilogramme  of  man  eliminating  in  twenty-four  hours  a 
quantity  of  urine  capable  of  killing  461  grammes  of  animal,  the 
proportional  part  of  the  mineral  matter  in  this  toxicity  may  be 
indicated  as  follows :  potass  kills  217  grammes ;  soda,  30 
grammes ;  calcium,  10  grammes ;  magnesia,  7  grammes.  The 
whole  of  the  mineral  matter  kills  264  grammes.  On  the  other 
side,  urea  kills  63  grammes.  There  remains  to  be  destroyed  134 
grammes.  We  know  from  other  experiments  that  normal  urine 
leaves  behind  in  charcoal  one-third  of  its  toxicity  ;  that  charcoal, 
consequently,  retains  matter  which  must  be  capable  of  killing 
154  grammes.  Amongst  these  substances  fixed  in  charcoal 
there  is  one-sixteenth  of  the  total  potass  ;  this  fraction  of  potass 
would  kill  14  grammes.  The  organic  substances  capable  of 
being  fixed  by  charcoal  would  therefore  be  capable  of  killing 
140  grammes.  This  figure  passes  by  6  be3'ond  the  134  grammes 
which  remain  to  produce  intoxication.  That  is  due  to  errors 
inherent  in  all  these  estimates;  the  cause  of  it  maybe  in  the 
charcoal  being  able  to  fix  a  part  of  the  urea  or  some  mineral 
matter  other  than  potass ;  it  may  finally  be  explained  by  the 
urine  containing  poisona  which  are  antagonistic, — a  fact  which 
we  have  placed  beyond  doubt. 

We  may  say  that  1  kilogramme  of  man  eliminates  in  twenty- 
four  hours  organic  matter,  capable  of  being  fixed  by  charcoal, 
which  is  able  to  destroy  at  least  134  grammes  of  animal.  These 
substances  (coloring,  extractives,  or  alkaloids)  represent  30 
per  cent,  of  the  total  toxicity.  It  is  to  these  substances,  still 
undetermined,  that  hereafter  the  effort  of  chemistry  should  be 
directed.  We  know  of  them  only  what  physiology  has  taught 
us, — the  one  contracts  the  pupil,  another  is  convulsive,  and  the 
third  lowers  the  temperature.  Chemistry  will  also  have  to  iso- 
late, in  the  alcoholic  extract,  the  narcotic  substance  and  the  sali- 
vating, which  is  perhaps  toxic.  I  have  thought  that  the  alkaloids 
will  only  explain  a  very  small  portion  of  these  30  per  cent,  of  the 
toxicity  attributable  to  undetermined  bodies. 

In  any  case,  we  have  come  to  this  conclusion  :   It  is  that  the 


126  LECTURES   ON   AUTO-INTOXICATION. 

whole  of  the  mineral  substances  reckon,  at  the  most,  as  57  per 
cent,  of  the  urinary  toxicity,  and  that  potass  explains,  at  the 
most,  47  per  cent,  of  this  toxicity.  Thus,  uraemia  comprises  vari- 
ous and  multiple  intoxications,  to  which  are  attributable  various 
symptoms.  It  is  a  mixed  poisoning,  not  by  urine  (as  one  calls 
it  by  misapplication  of  words),  but  by  what  should  have  become 
urine  ;  for  the  accidents  from  the  retention  of  urinary  substances 
are  not  those  from  the  re-absorption  of  urine.  The  sources  of 
uraemia  are:  disassimilation,  a  certain  number  of  secretions, 
alimentation, — especially  the  alimentary  mineral  substances, — 
and,  lastly,  intestinal  putrefactions.  The  knowledge  of  these 
origins  of  uraemia  furnishes,  as  we  shall  see,  valuable  indications 
from  the  point  of  view  of  treatment. 


LECTURE  XV. 

THE  THERAPEUTIC   PATHOGENESIS  OP  URAEMIA. 

Resumt  of  the  pathogenesis  of  uraemia  considered  as  a  complex  intoxication  and 
due  to  poisons  resulting  from  disassimilation,  furnished  by  alimentation,  the 

biliary  secretions,  and   intestinal  putrefactions. The   renal   emunction, 

having  become  insufficient,  may  be  supplemented  by  other  apparatus, — the 
skin  and  lung  ? Baths  of  hot  and  dry  air ;  vapor  baths.  Sudorific  medica- 
ments. These  methods  have  the  fault  of  diminishing  the  renal  secretion. 

Means  destined  to  arouse  the  renal  function,  either  by  reducing  congestion  of 
the  kidneys  (revulsives,  cupping,  sinapisms)  or  by  accelerating  ,reflexly  the 
renal  circulation  (utility  of  dry  cutaneous  friction).  Action  of  medicaments 
called  diuretics  (caffeine,  digitalis).  Indications,  counter-indications,  and 
management  of  digitalis  in  nephritis.  Cold  injections  as  a  diuretic ;  cool 

drinks.     Urea  as  a  diuretic  medicine. Can  we  supplement  the  kidney  by 

utilizing,  as  an  emunctory,  the  mucous  membranes  of  the  digestive  canal  ? 
Vomitings  :  their  inconveniences.  Purgatives  :  the  dehydration  of  the  tissues 

which   they  produce  may  become  dangerous. Of  bleeding  :  it  removes 

from  the  blood  one-sixteenth  of  the  extractive  material  which  the  urine 
ought  to  throw  out.  A  bleeding  of  32  grammes  removes  as  much  poison  as 
280  grammes  of  diarrhoeic  liquid,  and  as  100  litres  of  perspiration.  Utility 
of  bleeding  supported  by  clinical  experience.  Its  formal  indication  in 
acute  curable  nephritis.  Its  employment  owing  to  its  being  the  best  and  a 

rapid  expedient  in  the  terminal  uraemia  of  chronic  nephritis. Antidotes 

to  uraemic  poisons.  Inhalations  of  chloroform.  Action  of  chloral.  Bromide 
of  sodium.  Traditional  and  pathogenic  therapeutics.  Milk  regimen  to 
diminish  biliary  secretion  and  to  prevent  putrescible  intestinal  residues. 
Charcoal  as  the  means  for  fixing  the  coloring  matter  of  the  bile.  Interdic- 
tion of  roast  meat,  aliments  rich  in  extractive  and  mineral  matter,  soup. 
Diet  composed  of  milk,  white  of  egg,  cheese,  boiled  meat.  Disinfection  and 
intestinal  antisepsis  with  iodoformized  charcoal  and  naphthalin.  Agree- 
ment between  the  means  which  experiment  has  ratified  and  those  which  are 
the  outcome  of  a  study  of  pathogenesis. 

I  REGARD  unemia,  then,  as  a  complex  poison,  to  which,  in 
unequal  proportions,  all  the  poisons  introduced  normally  into 
the  organism  or  found  therein  physiologically  contribute,  when 
the  quantity  of  poison  formed  or  introduced  in  twenty-four  hours 
can  no  longer  be  eliminated  in  the  same  time  by  the  kidneys, 
which  have  become  scarcely  sufficiently  permeable.  This  view, 
the  legitimacy  of  which,  I  think,  I  have  experimentally  demon- 
strated to  you,  differs,  to  a  certainty,  from  the  old  doctrines  and 

(12T) 


128  LECTURES   ON   AUTO-INTOXICATION. 

even  from  those  which  still  prevail  to-day,  since  each  one  of  them 
endeavors  to  attribute  to  the  action  of  one  substance  alone  all  the 
accidents  called  uraemic.  Between  the  best  of  these  opinions — that 
which,  self-recommended  by  the  name  of  Schottin,  incriminates 
the  whole  group  of  extractive  substances,  an  opinion  which  M. 
Jaccoud  designates  under  the  theory  of  creatinsemia — and  that 
which  I  have  proposed  there  is  still  this  difference,  viz,  that 
•Schottin  and  the  partisans  of  his  theory  have  only  regarded  as 
toxic  agents  the  substances  which  originate  from  disassimila- 
tioii ;  but  to  me  this  is  only  one  of  the  sources  of  the  produc- 
tion of  the  toxic  bodies,  and  it  is  necessary  to  add  to  them  the 
poisons  furnished  by  the  biliary  secretion,  alimentation,  and 
intestinal  putrefactions. 

The  pathogenetic  theory  which  I  admit  is,  then,  more  com- 
prehensive than  its  predecessors.  Uraemia  is  to  me,  I  repeat, 
intoxication  by  all  the  poisons  which,  normally  introduced  into 
or  found  in  the  organism,  ought  to  have  been  eliminated  by  the 
renal  path,  and  are  prevented  from  being  so  owing  to  the  im- 
permeability of  the  kidneys. 

Such  a  conception  has  led  to  therapeutic  views  which  appear 
to  me  not  to  be  deprived  of  interest.  But  before  approaching 
them  I  ought  to  treat  the  question  of  the  possible  supplanting 
of  the  kidney  by  other  eliminating  organs.  We  have  really,, 
for  a  long  time,  thought,  in  cases  where  the  renal  apparatus 
fails,  to  accomplish  its  depurative  acts,  of  causing  it  to  be  sup- 
planted by  other  organs,  such  as  the  skin  and  lungs.  Thus 
we  have  given  to  those  suffering  from  uraemia  baths  of  hot  and 
dry  air;  we  have  proposed  by  this  means  to  introduce,  at 
each  inspiration,  a  certain  quantity  of  dry  air,  which,  expelled 
during  expiration  ladened  with  moisture,  removes  in  this  way 
water  from  the  organism.  We  have  also  tried  to  induce  depri- 
vation of  water  from  the  economy  by  increasing  the  perspira- 
tion, either  by  administering  vapor  baths  or  by  the  employment 
of  sudorific  medicines,  such  as  jaborandi.  In  all  these  cases 
we  certainly  remove  something  from  the  blood,  but  not,  unfor- 
tunately, that  which  is  toxic.  We,  perhaps,  remove  from  the 
economy  certain  toxic  substances  which  ought  normally  to 
depart  by  the  skin,  but  not  those  which  the  kidney  is  charged 


THE   THERAPEUTIC   PATHOGENESIS   OF   UREMIA.  129 

with  the  duty  of  eliminating.  What  we  specially  remove  from 
the  organism  by  this  means  is  water.  The  inevitable  result  is 
diminution  of  the  quantity  of  urine  ;  and  it  is  difficult  for  me  to 
admit  that  this  diminution  of  urine  is  a  useful  result  in  the  case 
of  patients  whose  urine  is  already  diminished,  both  as  regards 
quantity  and  specific  gravity. 

The  question  might  be  more  logical!}'  raised  when  it  is  pro- 
posed to  increase  the  secretion  of  urine  by  various  means.  Some- 
times we  have  attempted  to  diminish  the  congestive  state  of  the 
kidney,  either  in  acute  diseases  or  in  cases  of  congestive  exacer- 
bations arising  in  the  course  of  chronic  affections  of  this  organ, 
b}T  means  of  revulsives  (wet  or  dry  cupping,  leeches,  sinapisms). 
Sometimes  we  are  obliged  to  stimulate  the  nervous  sj-stem  by 
irritating  its  cutaneous  branches  by  friction,  in  order  to  obtain, 
in  a  reflex  manner,  a  quickening  of  the  renal  circulation  and, 
consequently,  an  increased  secretory  activity  of  the  kidney.  I 
am  convinced  that,  in  manj'  cases,  cutaneous  friction  increases 
urinary  secretion.  We  have  demanded  the  same  result  for  cer- 
tain medicines,  caffeine  and  digitalis  especially, — means  differing 
from  the  preceding,  since  they  are  applied  to  the  central  nervous 
system.  Apropos  of  digitalis,  I  cannot  refuse  to  tell  }-ou  that 
this  medicine  ought  not  to  be  indifferently  emplo3red  at  all  pe- 
riods in  diseases  of  the  kidney.  When  the  function  of  the  kid- 
ney is  impeded  it  is  prudent  to  use  only  with  extreme  caution 
certain  medicines.  When  the  impermeability  of  the  kidney  has 
become  such  that  it  ceases  to  have  the  power  of  eliminating 
toxic  substances  formed  by  the  organism,  there  is  then  retained 
the  medicinal  substances ;  the  kidney  is  as  impermeable  for 
therapeutic  poisons  as  for  natural  poisons,  and  the  emplo3'ment 
of  toxic  medicines,  in  similar  cases,  has  no  other  effect  than  to 
bring  about  an  association  of  medicinal  intoxication  with  a 
ursemic. 

Digitalis  succeeds,  however,  in  certain  cases  of  Bright's  dis- 
ease, in  increasing  the  quantity  of  urine,  but  it  is  chiefly  so  when 
there  are  cardiac  disorders  associated  with  disease  of  the  kidney, 
and  when  this  organ  has  not  become  very  impermeable;  at  a 
period  more  advanced  we  ought  to  dread  the  action  of  digitalis. 
I  do  not  say  that  it  is  absolutely  necessary  to  renounce  it,  but 


130  LECTURES  ON   AUTO-INTOXICATION. 

it  is  necessary  to  watch  the  administration  of  it  very  carefully. 
Prudence,  moreover,  does  not  consist  in  using  small  doses  only  ; 
we  must  employ,  on  the  contrary,  sufficiently  large  doses, — doses 
which  run  the  risk  of  being  toxic, — without  which  we  would  not 
obtain  any  result ;  but  these  doses  ought  to  be  sufficiently  small 
so  that  we  may  have  time  to  immediately  suppress  the  adminis- 
tration of  the  drug  if  there  appear  signs  of  intolerance,  nausea, 
or  vomiting.  It  goes  without  saying  that  digitalis  is  inapplicable 
in  that  form  of  uraemia  which  is  characterized  clinically  by 
gastro-intestinal  accidents. 

There  are  yet  other  means  of  increasing  the  quantity  of  urine. 
We  may  propose  the  displacement  of  a  part  of  the  mass  of  blood, 
which  is  in  relative  stagnation  in  certain  parts  of  the  vascular 
system,  and  to  throw  it  into  the  main  circulation,  in  order  to 
increase  the  pressure  within  the  vessels  of  the  kidney.  Between 
the  arterial  capillaries  of  the  abdomen  and  the  liver  is  found 
quite  a  considerable  mass  of  blood  accumulated  in  the  portal 
system  and  in  the  hepatic  and  splenic  parenchyma;  we  may 
throw  that  reserve,  nearly  stagnant,  into  motion  in  the  general 
circulation ;  we  may  empty,  in  a  word,  the  portal  system,  in 
order  to  augment  the  general  arterial  tension  and,  in  conse- 
quence, set  the  renal  function  agoing.  This  result  may  be  ob- 
tained by  the  introduction  of  cold  water  into  the  abdomen,  by 
the  employment  of  cold  injections.  I  have  seen,  in  certain  cases, 
a  grave  anuria  disappear  by  the  use  of  cold  injections ;  it  is 
therefore  a  means  we  ought  not  to  neglect.  We  may  carry  in 
cool  drinks,  which,  besides  the  stimulation  which  they  impress 
upon  the  contractility  of  the  abdominal  vessels,  will  induce  ab- 
sorption of  a  certain  quantity  of  water,  in  order  still  to  increase 
diuresis.  Amongst  the  liquids  which  it  is  usual  to  prescribe, 
milk  is  one  of  the  most  powerful  medicaments  which  we  can  op- 
pose to  uraemic  accidents,  and  not  only  to  albuminuria.  Its 
advantages  are  numerous,  as  we  shall  see. 

We  can  also  utilize  as  a  medicament  a  body  which  has  been 
considered,  until  to-day,  a  poison,  and  which  is  capable,  more 
than  any  other,  of  encouraging  the  secretion  of  urine.  I  am 
now  speaking  of  urea,  to  which  we  certainly  cannot  attribute 
the  accidents  of  uraemia,  and  which,  on  its  own  side,  even  com- 


UREA   AS   A   DIURETIC.  131 

bats  them  by  forcing  the  renal  barrier.  In  animals,  urea  has 
been  experimentally  demonstrated  to  be  a  diuretic.  In  a  healthy 
man,  ingested  by  the  gastric  mucous  membrane,  it  has  not  ap- 
peared to  increase  the  quantit}r  of  urine.  It  would  therefore 
remain  to  be  determined  whether,  in  a  sick  person,  by  subcu- 
taneous injections  of  urea,  we  could  succeed  in  increasing  the 
urinary  secretion.  I  have  undertaken  in  animals,  and  more 
lately  in  men,  experiments  bearing  upon  this  point.  In  a  patient 
with  Bright's  disease,  the  subject  of  a  cardiac  affection,  I  have 
once  seen  the  subcutaneous  injection  of  urea  induce  a  diuresis 
of  7  litres  in  twentj'-four  hours ;  but  I  ought  to  say  that  in  the 
renewed  relapses  of  oliguria  in  this  same  patient  the  injection 
of  urea  has  failed,  as  has  also,  at  other  times,  the  administration 
of  digitalis,  which  some  weeks  previously  had  abundantly 
induced  diuresis. 

I  have  established  that  the  skin  and  the  lung  cannot  vicari- 
ously aid  the  kidney  which  has  become  incapable  of  accomplish- 
ing its  task  of  elimination.  But,  have  other  emunctories  the 
power?  Or,  at  least,  can  we  not  utilize  as  emunctories  large 
mucous  surfaces,  such  as  that  of  the  digestive  canal,  the  stom- 
ach, and  intestine? 

For  a  long  time  we  have  combated  uraemia  by  inducing  vomit- 
ing. We  have  sought  to  imitate  what  occurs  in  certain  cases  of 
uraemia  in  which  vomiting  is  frequent ;  it  is  therefore  proposed  to 
provoke  a  secretion  of  extractive  matter  from  the  surface  of  the 
stomach.  It  is  not  shown  that  the  vomiting  notably  increases 
the  gastric  secretion.  It  1ms,  on  the  contrary,  two  evident 
inconveniences :  it  produces  two  effects, — lowering  of  arterial 
tension  and,  in  consequence,  diminution  of  renal  secretion  ;  and 
increase  of  the  cutaneous  secretion,  which  further  diminishes 
the  renal  secretion.  Besides,  some  have  quickly  given  up  this 
practice,  and  have  had  recourse  to  the  intestine,  in  which  the}' 
have  provoked  l^-persecretion  by  drastic  purgatives.  Purgatives 
have  been  employed  for  a  very  long  time,  in  accordance  with 
theoretical  views.  It  is  upon  the  theoiy  of  Wilson  that  phy- 
sicians have  relied,  who  have  wished,  by  means  of  purgatives, 
to  remove  urea  from  the  blood  ;  but  the  intestinal  secretion  has 
no  elective  action  upon  urea ;  it  only  removes  urea  from  the 


132  LECTURES   ON   AUTO-INTOXICATION. 

blood  ill  the  proportion  in  which  it  is  found  in  the  blood-plasma. 
If  the  serum  of  blood  contains,  per  litre,  32  centigrammes  of 
urea,  the  liquid  which  exudes  into  the  intestine  under  the  influ- 
ence of  purgatives  contains  exactly  32  centigrammes  of  urea 
per  litre. 

On  the  other  hand,  if  we  remove  one  litre  of  water  from  the 
blood  by  the  intestinal  tract,  it  is  simply  a  litre  of  water  less 
that  will  pass  away  by  the  renal  path ;  but  this  litre  of  water, 
eliminated  as  urine,  could  have  removed  fifty  times  more  urea. 
In  addition,  we  know  that  the  theory  of  Wilson  is  wrong,  and 
that  urea  is  not  the  cause  of  the  uraemic  accidents. 

Let  us  see  what  is  the  composition  of  the  substances  elimi- 
nated by  purgatives,  only  considered  as  poisonous.  Purgatives 
remove  from  the  blood,  in  the  first  place,  water ;  they  dehydrate 
the  blood  and,  consequent!}',  the  tissues;  this  dehydration,  per- 
haps, causes  a  diminution  of  cedemas  and  effusions  into  serous 
cavities;  this  will  remove,  perhaps,  water  from  the  cells  and, 
along  with  this  water,  a  portion  of  toxic  material.  But  there 
will  only  result  from  this  a  favorable  effect  if  we  immediately 
restore  to  the  tissues  the  water  which  we  have  just  removed; 
otherwise,  we  shall  have  only  displaced  the  poison  by  making  it 
pass  from  the  cells  into  the  plasma ;  after  dehydration  it  is 
necessary  to  bring  about  immediate  hydration.  This  is  a  dan- 
gerous game ;  we  are  never  sure  of  being  able  to  graduate  at 
will  these  alternatives  of  subtraction  and  restitution  of  water 
from  the  blood  an,d  tissues. 

Nevertheless,  I  do  not  wish  to-  proscribe  a  method  in  favor 
of  which  clinical  experience  seems  to  have  decided  for  a  long 
time  past.  Diarrhoea  does  not  remove  urea  from  the  blood,  but 
it  removes  poisons  from  it.  In  an  adult,  in  good  health,  I  have, 
for  six  consecutive  days,  measured  the  urinary  toxicity,  in 
periods  of  four  hours.  The  curve  of  the  toxicity  is  reproduced 
each  day,  regularly  and  always  at  the  same  time.  But  I  have 
established  a  disturbance  coincident  with  a  diarrhoea.  During 
the  four  hours  coincident  with  this  diarrhoea,  urinary  toxicity 
had  undergone  notable  diminution.  I  have  thought  that  the 
poisons  which  were  then  awanting  in  the  urine  had  been  carried 
away  by  the  intestinal  fluid. 


BLEEDING   IN   UREMIA.  133 

We  have  until  now  only  discussed  means  that  are  injurious 
or  uncertain.  What  is  thought  of  bleeding?  What  happens 
when  we  remove  blood  from  a  uraemic  ?  In  removing  32  grammes 
of  blood  you  remove  from  it  50  centigrammes  of  extractive  sub- 
stances ;  the  daily  elimination  by  urine  is  8  grammes ;  you,  there- 
fore, in  this  way,  remove  one-sixteenth  of  the  extractive  sub- 
stances which  the  urine  ought  to  carry  away.  This  result  is 
not  insignificant ;  for,  if  the  kidney  ought  to  remove  in  one 
hour  these  50  centigrammes  of  extractives,  and  if  the  convulsive 
or  comatose  accidents  resulting  from  this  non-elimination  can 
kill  the  patient  during  this  hour,  the  bleeding  which  you  induce 
may  save  the  life  of  the  patient,  by  removing,  for  the  moment, 
from  him,  the  excess  of  toxic  material  which  causes  the  develop- 
ment of  fatal  accidents. 

In  an\r  case,  it  is  certain  that  we  remove  from  the  economy 
more  extractives  b}-  bleeding  than  by  any  other  channel,  the 
renal  tract  excepted ;  for  a  bleeding  of  32  grammes  removes 
from  it  as  much  as  280  grammes  of  a  liquid  diarrhoea  does,  or  as 
100  litres  of  perspiration.  Besides,  it  is  not  only  32  grammes 
of  blood — the  quantity  drawn  by  two  leeches — which  we  have 
removed  in  similar  cases.  Abercrombie,  Marshall  Hall,  Ra}'er, 
and  many  others  in  addition,  have  employed  copious  bleedings 
for  uraemic  accidents,  and  the}*  have  seen  patients  cured  who 
were  assuredly  threatened  by  death.  It  is  chiefly  in  acute  cura- 
ble nephritis,  such  as  scarlatinal  nephritis,  that  bleeding  finds  its 
formal  indication,  and  if  uraemic  accidents  arise;  for,  in  these 
cases,  the  renal  malady  only  demands  cure  when  the  patient 
does  not  succumb  to  the  fleeting  attack  of  uraemia.  In  these 
cases,  therefore,  it  is  obligator}-  to  practice  bleeding,  not  only 
because  it  is  theoretically  legitimate,  but  because,  practically,  it 
has  been  shown  to  be  useful. 

On  the  contrary,  in  chronic  diseases  of  the  kidney,  the 
utility  of  bleeding  is  doubtful.  We  cannot  incessantly  go  on 
bleeding  a  patient  with  uraemia  whose  kidney  is  definitively  and 
irrevocably  diseased  ;  we  should  only  hasten  death  by  impov- 
erishing his  blood.  There  is  scarcely,  therefore,  cause  for  prac- 
ticing bleeding  in  the  terminal  uraemia  of  chronic  nephritis, 
except  once,  viz.,  at  that  moment  when  accidents  threaten  inline- 


134  LECTURES  ON   AUTO-INTOXICATION. 

diate  death,  and  when  there  is  no  other  hope  than  of  delaying 
for  a  little  the  fatal  termination.  Since,  in  the  majority  of  cases, 
we  cannot  derive  great  benefit  from  bleeding,  we  have  thought 
of  employing  antidotes  capable  of  opposing  their  physiological 
effects  to  those  of  the  poisons  which  have  induced  the  uraemic 
attacks. 

Inhalations  of  chloroform  have  been  successful,  especially  in 
this  particular  intoxication,  which  singularly  resembles  uraemia, 
viz.,  in  the  eclampsia  of  lying-in  women.  The  evidence  of  their 
utility  has  not  been  so  great  in  the  uraemia  of  nephritis.  In 
every  case  they  find  their  application  only  in  the  convulsive  form, 
and,  of  course,  we  cannot  think  of  them  for  the  comatose  form. 
It  is  also  for  the  convulsive  variety  that  the  action  ol  chloral 
should  be  reserved,  of  which  we  do  not  otherwise  know  what  is 
its  exact  value  in  these  cases.  Bromide  of  potassium,  which  has 
also  been  proposed,  ought  to  be  rejected  at  once ;  for  it  can  of 
itself  determine  intoxication  by  the  potass  which  it  contains. 
If  we  wish  to  treat  uraemic  convulsive  accidents  by  bromide 
preparations  we  should  use  bromide  of  sodium ;  but  never 
should  we  employ,  in  uraemia,  any  salt  of  potassium,  no  more 
the  bromide  of  potassium  than  the  nitrate.  Under  other  condi- 
tions we  would  replace  them  with  advantage  by  the  bromide  and 
nitrate  of  sodium,  which  are  just  as  active  therapeutically  and 
forty  times  less  toxic. 

That  is,  therefore,  the  therapeutic  programme  for  uraemia, 
such  as  our  predecessors  have  bequeathed  to  us.  Amongst  all 
these  means,  what  of  worth  remains?  Certain  diuretic  agents, 
— first,  such  things  as  milk,  and  bleeding  for  certain  cases. 
Yet  perhaps  something  else  might  be  done  for  these  uraemic 
accidents  by  applying  the  pathogenic  therapeutics  which  I  have 
been  trying  to  put  in  favor  during  the  six  years  that  I  have 
lectured.  There  are,  perhaps,  therapeutical  indications  to  be  de- 
rived from  the  knowledge  we  possess  of  the  sources  of  the  accu- 
mulation of  toxic  substances  in  the  econonry, — disassimilation, 
the  secretion  of  the  liver,  alimentation,  and  intestinal  putrefac- 
tions. Let  us  see  if  we  cannot  act  upon  one  or  other  of  these 
sources  of  intoxication,  so  as  to  exhaust  or  diminish  them. 

Can  we  delay  disassimilation  ?     Is  there  any  indication  for 


THE  THERAPEUTIC  PATHOGENESIS  OP  UREMIA.        135 

administering  those  substances  which  have  the  reputation  of 
diminishing  the  exchanges  of  nutrition,  and  which  have  been 
called  the  medicines  that  save  the  wear  and  tear,  e.g.,  arsenic  and 
valerian  ?  It  would  be  quite  useless.  Disease  itself  has  produced 
this  arrest  of  disassimilation.  The  accumulation  of  toxic  sub- 
stances has  checked  the  condition  of  osmosis  ;  an  equilibrium  of 
tension  has  been  established  between  the  fluids, — intra-and  extra- 
cellular ;  the  circulation  of  matter  through  the  cell  no  longer  goes 
on,  except  imperfectly;  combustible  substances  and  the  heat-pro- 
ducing agent,  oxygen,  no  longer  enter,  but  with  difficulty,  into  the 
conflict, — so  little  that  we  see  the  temperature  fall,  an  evident 
proof  of  a  check  given  to  nutrition.  The  temperature,  taken  in 
the  rectum,  may  fall  to  30  degrees.  The  disease  itself  has  gone 
be}rond  the  point  wished  for  in  our  calculations.  It  is  useless, 
then,  to  think  of  impeding  further  oxidation,  whose  insufficiency 
may,  by  itself  alone,  become  fatal.  I  go  farther  :  those  things 
which  are  especially  toxic  are  the  products  of  life  without  oxygen. 
Increase  the  free  oxygen,  and  you  will  only  moderately  increase 
disassimilation,  but  the  products  of  this  disassimilation  will  be 
much  less  toxic.  I  have  seen  exposure  in  compressed  air  diminish 
by  more  than  one-half  urinary  toxicit}'.  It  is,  therefore,  rational 
to  adopt  the  practice  of  Jaccoud,  who  speaks  highly  of  the  inhala- 
tions of  oxygen  in  the  treatment  of  uraemia. 

What  can  we  do  to  combat  that  source  of  poison  which  is 
resident  in  the  biliary  secretion?  We  can  first  diminish  the 
quantity  of  bile  secreted.  A  means  used  empirically,  and  which 
is  excellent,  is  milk,  when  it  is  well  digested,  for  if  it  is  not 
absorbed  it  purges  and  increases  the  biliary  secretion.  But 
when  the  digestion  of  milk  is  perfect  constipation  is  established, 
and  the  dry  and  hard  faecal  residue  which  it  leaves  contains 
almost  no  biliary  pigment.  We  can  also  expel  bile,  when  it  has 
been  formed,  by  washing  it  out  by  the  help  of  certain  neutral 
salts,  whose  action  is  limited  to  making  it  force  its  way  rapidly 
through  the  intestinal  contents  as  far  as  the  anus.  You  will 
avoid,  in  every  case,  the  potass  purgatives, — soluble  cream  of 
tartar  and  the  salt  of  Seignette.  But  in  bile  the  greatest  part 
of  its  toxicity  rests  in  the  coloring  matter.  We  have  proof  that 
decolorized  bile  is  much  less  toxic.  We  have  the  means  of 


136  LECTURES  ON   AUTO-INTOXICATION. 

decolorizing  bile  in  the  digestive  canal  by  administering  char- 
coal in  sufficient  quantity. 

We  can  diminish  the  toxicity  which  is  resident  in  food- 
sources  by  diminishing,  from  this  point  of  view,  chiefly  their 
mineral  substances, — e.g.,  potass,  which  contributes  a  very  im- 
portant share  in  the  production  of  intoxication.  We  will 
choose,  for  ursemic  subjects,  food  that  is  quickly  digested  and 
absorbed,  and  which  will  also  have  the  advantage  of  not  handing 
over  to  the  agents  of  intestinal  putrefaction  undigested  and 
easily  putrescible  material.  We  will  search  for  foods  not  rich  in 
extractives  and  in  potass.  We  will,  then,  avoid  meat  and,  as  we 
have  done,  empirically,  for  a  long  time,  we  will  choose  milk,  which 
is  slightly  rich  in  potass,  and  which  has  proved  itself  satisfac- 
torily, from  so  many  points  of  view,  in  the  treatment  of  uraemia. 
We  will  add  to  this  the  white  of  egg,  and,  in  case  of  need,  cheese 
— which  no  longer  contains  the  soluble  mineral  matter  of  milk 
— and  boiled  meat ;  but  we  will  interdict  soup. 

Finally,  a  very  important  indication  is  to  prevent  intoxication 
caused  by  the  products  of  intestinal  putrefaction.  We  ought  to 
endeavor,  first,  to  admit  only  a  small  quantity  of  putrescible 
matter  into  the  digestive  canal,  so  that  the  digestive  residue 
may  form  solid  masses,  presenting  at  the  point  of  contact  with 
the  absorbing  mucous  membrane  only  surfaces  that  are  hard  and 
not  extensive.  The  past}'  residues  incessantly  mashed  by  the 
intestines,  on  the  contrary,  successively  allow  of  the  absorption 
of  the  poison  contained  in  their  superficial  and  deep  layers. 
Milk-food,  when  it  is  well  tolerated,  which  is  the  rule  when  milk 
is  ingested  in  small  quantities  and  well  broken  up,  produces  the 
desirable  result ;  that  is  to  say,  faecal  matter  scanty  and  solid. 
Thus,  from  whatever  point  of  view  we  regard  it,  milk  is  opposed 
to  all  sources  of  intoxication. 

We  can  still  fix  the  toxic  products  of  intestinal  putrefaction 
so  as  to  prevent  their  absorption.  Charcoal  gives  us  the  means 
of  doing  so.  We  may  even  oppose  putrefaction  itself  by  induc- 
ing intestinal  antisepsis.  We  possess,  in  the  association  of 
iodoform  in  charcoal,  and  in  naphthalin,  means  which  theoret- 
ically permit  us  to  practice  this  thoroughly.  Salicylate  of  bismuth 
may  be  employed  for  the  same  end,  and,  if  we  were  afraid  of  the 


BENEFICIAL    INFLUENCE   OF   INTESTINAL   ANTISEPSIS.  1ST 

passage  and  accumulation  in  the  blood  of  the  small  quantity  of 
salicylic  acid  absorbed,  we  might  substitute  for  it  the  subnitrate. 
In  fact,  my  colleague,  Dr.  Tapret,  has  applied  this  theoret- 
ical idea  to  the  treatment  of  uraemia,  and  he  has  thrice  seen 
ursemic  accidents  disappear  when  intestinal  antisepsis  had  been 
induced.  I,  myself,  have  seen  in  one  case,  formidable  ursemic 
d3-spncea  disappear  within  twenty-four  hours  after  the  adminis- 
tration of  naphthalin.  The  patient,  who  was  diabetic,  succumbed 
later  on  to  gangrene,  but,  to  a  certainty,  he  would  have  been 
dead  more  quickly  from  his  uraemia.  These  are  only  four  cases, 
but  they  are  encouraging,  especially  when  we  think  of  the 
small  number  of  therapeutic  means  at  our  disposal  for  treating 
uraemia. 

Thus,  to  resume,  diuretics  (and,  in  the  first  place,  milk: 
milk  as  food),  intestinal  antisepsis,  bleeding  for  accidents  imme- 
diately threatening,  and,  finally,  inhalations  of  oxygen, — that  is 
the  treatment  which  experience  has  confirmed.  It  is  also  that 
which  arises  naturally  from  the  conception  of  the  disease,  which 
we  have  admitted. 


LECTURE  XYI. 

TRANSITORY  OR  ACUTE   AUTO-!NTOXICATION  OP  INTESTINAL 
ORIGIN — INTERNAL  STRANGULATION  AND  CONSTIPATION. 

Increase  of  the  quantity  of  poison  contained  in  the  digestive  canal  when  there  is 
an  augmentation  of  the  activity  of  normal  fermentation.     Symptoms  and 

signs  of  the  increase  of  acid  fermentation  and  of  putrid  fermentation. 

Parallel  relation  between  the  increase  of  intestinal  fermentation  and  increased 
toxicity  of  urine.  Poisons  which  are  found  in  the  intestines  and  which  pass 
into  the  urine.  Phenol,  indol,  and  indican  ;  cresol.  Substance  which  gives  a 
claret  color  to  urine  after  the  addition  of  perchloride  of  iron,  but  which  is  not 

acetone. How  the  organism  is  protected  against  poisons  derived  from  the 

intestines.  Part  played  by  the  liver  from  the  point  of  view  of  the  arrest  and 
destruction  of  putrid  poisons.  Experiments  of  Schiff  and  of  G.  H.  Roger. 

Utility  of  hardening  the  intestinal  contents.     Role  of  auto-intoxication 

of  faecal  origin,  in  internal  strangulation  and  the  morbid  states  called  intes- 
tinal septicaemia  (Humbert).  The  two  periods  of  constipation  :  constipation 
with  retention  of  liquid  faecal  matter  causes  symptoms  of  intoxication,  and 
hardening  of  the  substances  renders  the  second  period  of  constipation  less 
harmful. 

WE  know  that  tbe  poisons  contained  in  the  intestines,  also 
those  which  come  from  food,  from  bile,  or  putrefaction,  enter,  on 
the  one  hand,  into  the  complex  intoxication  called  uraemia.  We 
can,  therefore,  understand  how,  if  the  quantity  of  poison  increase 
in  the  intestines,  an  intoxication  becomes  possible ;  at  the  same 
time,  that  disassimilation  does 'not  hand  over  to  the  blood  a 
larger  amount  of  toxic  material  even  when  the  kidney  remains 
permeable. 

To-day  we  are  going  to  study  intoxication  by  re-absorption 
of  substances  contained  in  the  digestive  canal,  without  the 
presence  of  other  pathological  states.  Experiment  has  proved 
to  us  that  the  toxicity  of  the  intestinal  contents  is  mixed,  and 
has  revealed  to  us  its  various  sources.  These  sources, — let  us 
recall  them : — 

1.  Foods — even  the  most  inoffensive  in  appearance — and  the 
flesh  of  muscle  are  toxic,  particularly,  on  account  of  the  mineral 
matter  and"  potass  principally.    We  have  shown  this  by  injecting 
aqueous  decoction  and  the  alcoholic  extract  of  meat. 
(138) 


AUTO-INTOXICATION   OP   INTESTINAL   ORIGIN.  139 

2.  Bile  contains  poison.     The  eight  hundred  or  one  thousand 
grammes  of  bile  which  are  turned  each  day  into  the  intestines 
of  an  adult  of  average  weight  are  toxic  on  account  of  the  color- 
ing matters  principally,  e.g.,  bilirubin,  and  also  other  substances: 
some  known, — such  as  the  biliary  salts, — others  unknown. 

3.  Putrefactions  which  develop  in  the  alimentary  residues 
engender  poison.     The  extract  of  2.5  grammes  of  putrefied  meat 
is  sufficient  to  kill. 

4.  Finally,  we  have  learned  that  faecal  matter  is  toxic ;  that 
this  toxicity  is  due  chiefly  to  potass  and  ammonia;  and,  on  the 
other  hand, — and  this  represents  about  one-fifth  of  the  total  tox- 
icity,— to  the  union  of  organic  principles,  in  which  are  included 
alkaloidal  substances. 

Thus,  the  paths  are  prepared  for  the  study  of  intoxication 
of  intestinal  origin,  since  we  know  that,  in  normal  conditions 
even,  there  is  material  for  intoxicating,  and  as  to  what  proportion 
each  of  the  poisons  shut  up  in  the  intestines  bears  to  the 
toxicity  of  the  whole. 

We  shall  now  see  how,  under  normal  conditions,  the  contents 
of  the  intestines  may  become  more  toxic,  and  how,  even  with  a 
kidney  functionally  free,  if  the  production  of  toxic  material  is 
accidentally  more  abundant,  it  may  yet  accumulate  in  the  blood 
in  a  proportion  capable  of  causing  S3rmptoms  of  intoxication  to 
arise.  When  fermentation  has  become  more  active  in  the  whole 
length  of  the  digestive  tube,  we  see  produced  a  succession  of 
phenomena  truly  characteristic.  The  unusual  development  of 
gas  determines  abdominal  meteorism  and  tympanites,  which  may 
be  from  the  stomach  or  intestines,  or  it  may  be  at  once  carried 
to  the  stomach  or  intestines.  The  disengagement  of  gas  reveals 
itself  by  eructations,  preceded  by  burning  sensations  in  the 
stomach,  or  accompanied  by  pyrosis  in  the  oesophagus  and 
ph.'irynx.  It  may  induce  acid  vomiting,  the  acidit}-  of  which  is 
most  frequently  due  to  acetic  acid v— rarely,  h}rdrocbloric.  The 
acidity  of  the  mouth  may  cause  changes  in  the  teeth.  The  con- 
tents of  the  intestines,  which  have  become  abnormally  acid,  may 
not  only  provoke  diarrhoea,  by  irritating  the  mucous  membrane, 
but  irritate  also  the  skin  outside  the  rectum,  as  witness  the 
erythema  of  the  bu.ttocks  in  the  acid  dyspepsias  of  infants.  An 


140  LECTURES  ON   AUTO-INTOXICATION. 

acid  reaction  is  substituted  for  the  normal  of  the  intestinal 
contents.  We  notice  changes  in  the  color  of  the  stools  :  bile  is 
expelled,  with  a  green  color.  The  production  of  sulphuretted 
hydrogen  is  diminished.  Certain  substances,  administered  with 
the  view  of  arresting  the  diarrhoea,  such  as  bismuth,  give  no 
longer  to  the  stools  a  black  color,  for  there  is  no  longer  formed 
sulphide  of  bismuth.  These  are  the  external  signs  which  indi- 
cate, even  to  the  naked  eye,  the  production  of  acid  fermentation 
in  the  digestive  canal. 

When  fermentation  of  a  putrid  character  predominates,  there 
is  produced  rather  an  excessive  disengagement  of 'sulphuretted 
hydrogen,  ammonia,  and  sulphate  of  ammonia,  which  reveal 
themselves  to  our  senses  by  the  odor  of  the  gas  expelled. 

Parallel  to  these  objective  phenomena  there  exist  those  of  a 
subjective  character,  amongst  which  the  most  ordinary  are  fatigue, 
depression,  headache,  buzzing  in  the  ear  and  deafness,  disturbances 
of  sight,  and  vertigo.  With  a  kidney  acting  well  things  may  not 
go  farther ;  but,  if  the  renal  emunction  is  insufficient,  we  ma}7 
see  developed  a  fraction  of  urasmic  intoxication  through  simple 
exaggeration  of  intestinal  fermentation.  If,  for  example,  abun- 
dant vomiting  has  caused  oliguria,  we  may  have  coldness  estab- 
lished, paralysis  of  the  vessels  of  the  skin,  cramps,  convulsions, 
coma,  paralyses,  death  even,  whilst  the  kidney  itself  may  not  be 
really  diseased.  It  will  be  sufficient  for  the  development  of  such 
accidents  that  the  quantity  of  toxic  material  introduced  into  the 
blood  should  exceed  the  activity  of  the  kidneys  charged  with 
the  function  of  eliminating  it. 

From  proof  of  the  preceding  facts,  we  can  already  con- 
clude that  the  quantity  of  urine  passed  is  very  important  in  the 
intoxication  of  intestinal  origin;  that  variations  of  urinary 
toxicity  may  be,  in  similar  cases,  the  measure  of  the  degree  of 
intoxication  ;  and  that  we  should  find,  under  the  influence  of 
intestinal  fermentation,  an  increase  in  the  toxicity  of  the  urine. 
I  have  known  that  in  a  large  number  of  diseases  it  is  thus.  If  I 
suppress  intestinal  fermentation,  I  cause  the  toxicity  of  urine 
to  diminish ;  I  cause  it  to  diminish,  but  not  to  disappear,  since 
I  only  suppress  one  of  the  natural  sources  of  its  toxicity.  I 
can  diminish  the  toxicity  of  urine  either  by  neutralizing  the 


INTESTINAL   SOURCE   OP   CERTAIN   POISONS.  141 

products  of  putrefaction,  by  the  aid  of  charcoal,  which  prevents 
their  absorption,  or  by  preventing  putrefaction  itself,  through 
causing  intestinal  antisepsis,  by  means  of  iodoform  and  naph- 
thalin.  I  have  thus  proved  the  reality  of  the  passage  of  a  larger 
quantity  of  toxic  material  from  the  intestines  to  the  kidnej'  in 
cases  where  there  has  been  an  increase  in  intestinal  fermentation. 

This  proof  had  already  been  given  formerly  by  chemistry.  In 
my  experiments  of  1882,  in  which  I  only  occupied  myself  with 
one  class  of  toxic  agents, — alkaloids, — I  had  shown  that  they 
increase  in  a  parallel  manner  in  the  faeces  and  in  the  urine.  I 
had  concluded  that  the  organism  is,  from  this  fact,  under  the 
risk  of  a  constant  menace  of  intoxication.  Other  observers  had 
preceded  me  in  this  path.  Stadeler,  in  1848,  had  found  phenol 
in  the  urine,  without  drawing  any  conclusion  from  it.  In  1877, 
Baumann  found  phenol  in  faecal  matter;  we  must  really  admit 
that  this  passes  from  the  digestive  tube  into  the  urine.  In  1826, 
Tiedemann  and  Gmelin  discovered  in  the  duodenum  a  substance 
which  gave  a  red  color  with  chlorinated  water, — indol.  Bracon- 
not,  without  noticing  in  his  discovery  any  relationship  with 
the  preceding,  has  shown  in  the  urine  the  existence  of  a  certain 
substance  of  a  different  color, — cyanurine, — which  is  indican 
derived  from  indol.  In  1872,  Jaffe  made  a  subcutaneous  injec- 
tion of  indol,  and  he  saw  that  indican  appeared  or  increased  in 
the  urine.  The  indol,  therefore,  which  is  formed  in  the  faeces  is 
the  cause  of  the  urinary  indican. 

These  early  experiments  are  the  source  of  all  that  have  been 
made  since  then.  A  very  convincing  experiment  is  that  of 
Senator.  He  seeks  for  indican  in  the  urine  of  the  newly-born, 
and  he  does  not  find  it ;  he  analyzes  the  meconium,  and  does 
not  find  indol  therein.  Nothing  is  better  shown  to-day  than  the 
parallel  relation  between  the  increase  of  indican  in  the  urine  and 
indol  in  the  faeces.  That  is  to  say,  variations  of  urinary  imlk-an 
according  to  the  activity  of  intestinal  fermentation.  Aloysius 
Martin  established  that  in  every  disease  of  the  intestinal  tube 
there  was  an  increase  of  urinary  indican.  Hassal  found  a 
large  proportion  of  it  in  the  urine  of  people  suffering  from 
cholera;  Gubler,  in  typhoid  fever  and  cholera.  One  of  Gnbler's 
pupils — A.  Robin — studied  its  variations  in  typhoid  fever. 


142  LECTURES  ON   AUTO-INTOXICATION. 

Carter  and  Jaffe  have  shown  that  urinary  indican  increases  in 
consequence  of  the  retention  of  faecal  matter  in  intestinal 
obstruction  and  in  internal  strangulation.  Senator  showed  the 
same  fact  in  certain  kinds  of  constipation ;  in  these  the  alvine 
secretions  are  maintained  in  a  liquid  or  semi-solid  state. 

Analogous  researches  have  been  made  for  other  substances 
by  Salkowsky, — for  phenol  and  cresol.  We  see  them  increase 
like  indican  in  the  urine,  in  certain  forms  of  diarrhoea,  and  in 
intestinal  obstruction.  I  will  say  the  same  of  a  substance,  not 
defined  chemically,  revealed  in  the  urine  by  a  claret  coloration 
induced  by  the  addition  of  perchloride  of  iron  to  it.  It  has 
been  observed  by  Senator,  Riess,  and  Litten,  not  only  in  aceton- 
semia  or  sugary  diabetes,  in  pernicious  anaemia  or  leucocy- 
thsemia,  but  in  grave  dyspeptic  states,  in  certain  cases  of  carci- 
noma of  the  stomach, — all  cases  in  which  anomalous  fermenta- 
tion is  produced  in  the  digestive  tube.  I  have  also  seen,  often 
enough,  this  coloration  of  urine  in  the  grave  forms  of  dilatation 
of  the  stomach,  in  cancer  of  the  stomach,  and  in  typhoid  fever. 
This  material  is  assuredly  not  acetone ;  it  is  analogous  to  it 
only  by  this  reaction  when  brought  into  contact  with  perchloride 
of  iron.  It  was  absent  in  certain  diabetics  whose  breath,  more- 
over, had  the  odor  of  acetone.  I  believe,  with  the  authors 
named  above,  that  it  is  frequently  found  related  to  increase  of 
fermentation  in  the  digestive  canal. 

All  these  substances,  known  or  suspected,  are  only  some  of 
the  products  of  intestinal  putrefaction,  but  they  show  very  well 
the  parallelism  between  the  entrance  of  putrid  matter  into  the 
blood  and  its  increase  in  the  urine.  We  know,  therefore,  that 
if  these  putrid  substances  are  formed  in  excess,  there  may  result 
from  them  an  intoxication  even  without  the  kidney  being  dis- 
eased. Nevertheless,  as  all  these  substances  exist  normally  in 
the  digestive  canal,  we  may  ask  whether  the  organism  has  no 
other  protection  against  them  than  the  kidney.  It  is  possible 
that  the  liver  may  give  this  protection,  and  that  the  experiments 
of  Schiff  relative  to  the  alkaloids  may  be  of  a  more  general  sig- 
nificance. This  hypothesis  may  rest  upon  some  experiments 
recently  performed  in  my  laboratory  by  G.  H.  Roger. 

The  alcoholic  extract  of  rotten  meat  is  twice  less  toxic  when 


SENTINEL   ACTION   OF   LIVER.  143 

we  inject  it  into  the  portal  vein  than  when  introduced  into  the 
general  circulation.  Extracts  of  the  intestinal  contents  of  the 
rabbit  and  the  dog  kill,  by  a  smaller  dose,  frogs  deprived  of  their 
liver,  than  healthy  frogs,  or  those  in  which  we  have  tied  the 
afferent  vessels  of  the  kidneys.  It  appears,  therefore,  to  be 
certain  that  the  liver  arrests  or  transforms  toxic  substances 
which  originate  in  the  intestinal  canal.  This  conception  again 
has  been  verified  experimentally :  blood  drawn  from  the  portal 
vein  of  the  dog  kills  a  rabbit  in  a  dose  of  from  13  to  14  cubic 
centimetres  per  kilogramme,  whereas  it  is  necessary  to  use  23 
cubic  centimetres  of  blood  removed  from  the  liver. 

These  recent  experiments  seem  to  lend  support  to  a  hypothe- 
sis put  forward  by  Schiff  now  a  long  time  ago.  You  know  that, 
in  consequence  of  an  abrupt  ligature  of  the  portal  vein,  the 
animal  falls  into  a  state  of  somnolence  and  dies  in  one  or  two 
hours,  if  it  is  a  dog ;  in  thirty  or  fort}7  minutes,  if  the  experi- 
ment has  been  performed  upon  a  rabbit.  Schiff  supposes  that 
the  death  is  due  to  an  intoxication  consequent  upon  the  reten- 
tion of  a  poison  which  the  liver  was  charged  with  the  function 
of  destroj'ing.  This  poison  would  originate  during  disassimila- 
tion,  and  Schiff  considers  that  he  has  demonstrated  its  existence 
by  the  following  experiment :  He  removes  the  liver  from  a  frog, 
the  animal  bearing  the  operation  well ;  that  is,  without  immedi- 
ate death.  He  injects  into  it  blood  removed  from  a  healthy 
dog ;  the  frog  does  not  die.  He  ties  the  portal  vein  of  this  dog, 
which  falls  into  somnolence  and  dies.  He  takes  some  blood 
from  this  dog  and  injects  it  into  the  frog  ;  this  becomes,  in  its 
turn,  somnolent,  and  dies,  at  the  end  of  from  half  an  hour  to  an 
hour. 

The  experiment  has  been  repeated  in  my  laboratory  by  M. 
Roger;  he  has  injected  into  rabbits  the  blood  of  a  dog,  before  and 
after  ligature  of  the  portal  vein.  In  these  two  cases  the  toxicity 
has  been  the  same,  viz.,  25  cubic  centimetres  per  kilogramme. 
This  result— completely  opposed  to  that  of  Schiff— does  not 
cause  me,  in  any  way,  to  repudiate  the  idea  that  the  liver  arrests 
and  is  constantly  transforming  toxic  products  ;  the  comparative 
toxicity  of  the  portal  and  hepatic  blood  demonstrates  it.  Only, 
in  the  experiment  of  Schiff,  poisoning  has  no  time  to  be  pro- 


144  LECTURES   ON    AUTO-INTOXICATION. 

duced  ;  the  animal  appears  to  succumb,  as  Claude  Bernard  has 
said,  to  an  intestinal  hyperaemia  and  consequent  cerebral 
anaemia.  In  order  to  study  auto-intoxication,  after  suppressing 
the  function  of  the  liver,  it  will  be  necessaiy  to  join  together 
the  portal  vein  and  the  renal.  The  experiment  made  by  Holni- 
kew,  from  another  point  of  view,  has  allowed  the  animal  to  live 
from  eight  to  ten  hours. 

I  think  that  we  may,  therefore,  conclude  that  the  liver  is  an 
organ  of  protection  to  the  economy ;  that  it  arrests  more  or 
less  of  the  toxic  material  in  general, — not  the  whole,  since  a  part 
passes  into  the  urine.  The  liver  is  certainly  not  the  only  agent 
which  acts  the  part  of  protector  to  the  organism  against  poisons. 
There  may  yet  be  made  to  intervene,  as  an  auxiliary  agent  of 
protection,  rapidity  of  intestinal  expulsion  by  the  stools, — hard- 
ening of  the  intestinal  contents,  which,  transformed  into  a  hard, 
faecal  bolus,  becomes  almost  inoffensive,  because  it  no  longer 
allows  of  absorption. 

After  having  admitted  this  hypothetical  and  theoretical 
mechanism  of  intoxication  by  poisons  of  intestinal  origin,  let 
us  see  if  there  exist,  really  and  clinically,  such  intoxications. 
On  this  point  I  shall  borrow  from  the  teaching  laid  down  in  the 
work  of  M.  Humbert,  who  has  used  the  word  intestinal  septi- 
caemia in  the  sense  of  intoxication.  I  find  therein  startling 
examples  of  intoxication  in  some  of  the  phenomena  which  are 
produced  in  the  course  of  surgical  affections  causing  intestinal 
obstruction.  In  the  first  place,  mechanical  phenomena  are 
demonstrated  by  the  arrest  of  matter,  pain  complained  of  above 
the  obstacle,  and  abdominal  distension.  Then  reflex  actions : 
vomiting  which  cannot  be  attributed  to  intoxication,  fall  of 
arterial  tension,  frequency  of  the  pulse,  perspiration,  etc.  All 
these  reflexes  are  often  arrested  at  the  end  of  one  or  two  days, 
and  during  these  two  days  vomiting  ceases.  Then  appears  a 
new  phase,  characterized  by  prostration  and  collapse, — a  par- 
ticular pallor  of  the  skin,  not  pale,  owing  to  spasm  of  vessels, 
but  earthy-looking,  from  being  impregnated  with  coloring 
matter;  coldness,  and  muscular  cramps.  Humbert  asks  whether 
a  part  of  this  complicated  clinical  picture  should  not  be  attrib- 
uted to  intoxication.  We  must  certainly  reply  to  him  in  the 


AUTO-INTOXICATION    OF   INTESTINAL   ORIGIN.  145 

affirmative.  Why  this  period  of  respite?  It  is  inexplicable  on 
the  theory  of  reflexes.  It  finds,  on  the  contrary,  an  explanation 
in  intoxication.  Examination  of  the  aforementioned  facts  does 
not  offer  to  us,  doubtless,  a  true  demonstration,  but  it  forces  us  to 
consider.  It  is  not  uncommon  to  observe  cases  of  strangulated 
hernia  in  which  accidents  continue  when  the  intestinal  strangu- 
lation has  been  relieved,  because  putrid  material  is  freely  spread 
throughout  the  whole  length  of  the  digestive  tube,  which 
absorbs  it. 

An  objection  often  made  to  the  hypothesis  of  intoxication 
of  faecal  origin  is  the  fact  that  constipation  is  compatible  with 
health.  If  this  hypothesis  were  true,  say  some,  intoxication 
would  be  realized  to  the  full  in  constipated  people.  I  reply 
that  constipation  ought  to  be  regarded  as  a  protection  against 
intoxication.  It  supposes  that  all  that  is  absorbable  has  been 
absorbed,  the  aqueous  part  with  what  was  held  in  solution. 
In  constipation  there  is,  at  first,  a  preliminary  phase,  in  which 
appears  a  threatening  of  intoxication,  but,  in  the  second  place, 
intoxication  is  no  longer  in  operation. 

Besides,  are  constipated  people  healthy  ?  They  have  head- 
ache, migraine,  and  vertigo.  Hypochondriacs,  whose  suffer- 
ings are  chiefly  subjective,  are  constipated.  They  experience  a 
number  of  nervous  disorders  of  sensibility,  buzzing  in  the  ears 
and  psychical  troubles.  All  the  insane  are  constipated,  and  alien- 
ists endeavor  specially  to  guard  against  constipation.  I  do  not 
say,  of  course,  that  psychical  troubles  are  caused  by  constipation. 
I  only  say  that  they  are,  in  a  certain  sense,  exaggerated  by  it. 
I  say  that  the  nervous  system  is  maintained  in  a  condition  of 
hurtful  disposition  by  constipation,  and  that  we  render  a  service 
to  patients  attacked  by  cerebral  troubles  when  we  cause  to  dis- 
appear, at  the  same  time  as  constipation,  the  unhealthy  disposition 
of  the  nervous  system. 

Thus  we  see,  in  the  two  examples  of  septicremia  of  Humbert, 
and  of  constipation,  the  maximum  and  the  minimum  of  accidents 
attributable  to  the  intoxication  of  intestinal  origin. 


LECTURE  XVII. 

ACUTE  OR  TRANSITORY  INTESTINAL  AUTOINTOXICATION — GASTRIC 
DISORDERS— INDIGESTION — POISONING  BY  TAINTED  MEATS. 

Explanation  of  the  symptoms  of  gastric  disorder  from  retention  of  toxic  material 
in  the  stomach.  Washing  out  of  the  stomach  in  certain  forms  of  intestinal 
obstruction.  Indications  for  emptying  the  intestines  in  surgery  and  obstet- 
rics.  Indigestion,  with  excessive  production  of  toxic  matter  in  the  digest- 
ive canal.  Presence  of  sulphuric  acid  in  the  intestines  and  emunctories  in 
a  case  of  grave  indigestion  (Senator).  Case  of  indigestion  with  enormous 

quantity  of  alkaloids  in  the  intestines  and  urine. Poisoning  by  tainted 

meats :  old  sausages.    The  epidemic  at  Andelflngen.    Why  these  morbid 
states  are  intoxications  and  not  infections. 

I  HAVE  just  shown  you,  in  internal  strangulation  and  m  con- 
stipation, the  two  extremes, — the  maximum  and  the  minimum  of 
intoxication  of  intestinal  origin.  In  the  morbid  state — still 
badly  known — which  we  call  acute  dyspepsia  things  are,  at 
their  origin,  obscure  and  complex.  We  do  not  know  what  is 
the  primary  cause  of  gastric  fullness,  but  we  do  know  that 
there  exists  in  this  affection,  at  a  given  moment,  a  diminution 
of  the  secretions ;  of  the  saliva,  whence  the  clammy  state  of  the 
mouth;  of  the  gastric  juice,  whose  peptogenetic  power  is  weak- 
ened ;  of  the  intestinal  glands,  which  causes  constipation.  The 
appetite  is  diminished,  and  that  is  very  advantageous,  since  the 
digestive  power  is  less,  and  also  because  the  taking  of  food  in  as 
large  a  quantity  as  under  ordinary  conditions  would  transfer  to 
parasitic  ferments  more  putrescible  material.  In  these  condi- 
tions of  imperfect  digestive  secretions  I  see  the  possibility  of  a 
development  of  anomalous  fermentations.  It  is  certain  that  the 
subjective  troubles  felt  by  patients  cannot  be  explained  by  an 
insufficient  alimentation  of  so  short  a  duration.  On  the  con- 
trary, the  production  of  putrid  fermentations  explains  the  bitter- 
ness felt  in  the  mouth,  headache,  and  depression.  If  I  have  not, 
therefore,  any  information  as  to  the  primary  cause  of  the  dis- 
ease, I  have  reasons  for  supposing  that  one  part  ought  to  be 
attributed  to  intoxication  in  the  pathogenesis  of  some  of  the 
accidents. 

(146) 


WASHING   OUT   OF   STOMACH.  .  Ht 

In  certain  individuals  habitually  the  subjects  of  diarrhoea, 
who  have,  nevertheless,  during  each  day,  only  one  liquid  and 
fetid  stool,  we  observe  nearly  always  headache,  vertigo,  and  some 
shivering.  They  in  general  experience  bitterness  in  the  mouth ; 
their  breath  and  their  skin  have  a  disagreeable  odor.  But  all 
these  inconveniences  may  disappear  for  a  time  by  evacuating  the 
contents  of  the  large  intestine.  The  individual  who  awakens 
with  a  sensation  of  lassitude  ma}'  be  deprived  of  it  l>y  a  simple 
injection.  What  I  say  to  you  in  regard  to  this  does  not  consti- 
tute a  demonstration,  but  it  is  more  a  reason  for  adding  to  the 
probabilities  in  favor  of  the  part  played  by  intoxication  in  the 
genesis  of  troublesome,  though  attenuated,  nervous  symptoms, 
apart  from  any  completely-established  disease. 

We  may  see  more  severe  symptoms  yield  after  simple  evacua- 
tion of  the  contents  of  the  digestive  canal.  Washing  out  of  the 
stomach  is  not  a  curative  means,  properly  speaking;  but  it 
removes  certain  forms  of  malaise,  headache,  and  migraine.  In 
certain  patients,  the  subjects  of  dilatation  of  the  stomach,  lavage 
causes  not  only  the  disappearance  of  pain,  pyrosis,  and  heart-burn, 
but  all  the  other  accidents  called  reflex.  Assuredly,  washing 
out  does  not  cure  dilatation  of  the  stomach,  but  it  is  in  certain 
cases  necessary,  and  it  renders  considerable  service  in  weaken- 
ing the  most  painful  symptoms, — services  which  are  manifest, 
but,  unfortunately,  also  transitory.  In  my  clinique  was  :i  woman 
whose  stomach  was  dilated.  She  suffered  from  constant  supra- 
orbital  headache.  Washing  out  was  always  immediately  followed 
by  a  disappearance  of  this  headache. 

When  the  stomach  retains  substances  more  toxic,  which 
happens,  for  example,  in  intestinal  obstruction,  washing  out  has 
a  utility  no  less  observable.  Senator  had  formulated  this  indi- 
cation. M.  Chaiitemcsse  was  able  to  verily  the  reality  of  this 
in  a  patient,  in  my  service,  attacked  with  an  intestinal  obstruc- 
tion from  an  unknown  cause.  Faecal  vomiting  bore  witm-ss  t.» 
the  accumulation  of  toxic  material  in  the  stomach,  and  would 
explain  the  general  symptoms  which  accompany  intestinal  ob- 
struction :  the  small  pulse,  coldness,  owing  to  paralysis  of  the 
cutaneous  vessels,  etc.  Four  litres  of  a  horribly  fetid  liquid 
were  evacuated  by  means  of  the  cesophagcal  tube,  and  we  saw 


148  LECTURES   ON   AUTO-INTOXICATION. 

the  disappearance  of  symptoms  of  peritonism,  which  so  closely 
resemble  intoxication.  A  new  accumulation  of  faecal  matter 
was  followed  by  a  return  of  the  grave  symptoms,  which  evacu- 
ation of  the  contents  of  the  stomach  again  caused  to  disap- 
pear and  cured  the  individual.  He  was  cured  not  by  lavage, 
but  thanks  to  the  lavage,  which  gave  him  respite  by  arresting 
intoxication  and  in  giving  to  him,  I  presume,  time  for  the 
strangulation  to  free  itself.  There  are,  therefore,  cases  in  which 
toxic  accidents  caused  by  the  reflux  of  putrid  material  into  the 
stomach  have  disappeared,  thanks  to  lavage. 

There  are  other  circumstances  in  which  we  might  suppose  that 
stagnation  of  intestinal  material  causes  fever.  After  laparotomy 
the- fever  cannot  be  explained,  in  many  of  the  cases,  by  a  septic 
condition  of  the  peritoneum,  and  we  see  it  disappear  after  get- 
ting rid  of  constipation  (Kiistner).  Accoucheurs  know  quite 
well  how  certain  febrile  incidents  which  supervene  in  the  course 
of  parturition  disappear  after  alvine  evacuation,  either  sponta- 
neous or  induced  by  light  purgatives.  This  hurtful  influence  of 
the  stagnation  of  matter  in  the  intestines  after  operations  ex- 
plains old  traditions  forgotten  in  surgical  practice.  It  was  the 
rule  in  olclen  times  to  prepare  those  about  to  be  operated  upon 
by  administering  to  them  in  succession  an  emetic  one  day,  then 
on  the  following  day  a  purgative,  and  that  in  two  or  three 
takings.  We  no  longer  push  to  the  same  extent  to-day  this 
preventive  line  of  therapeutics ;  but,  the  operation  concluded, 
unless  it  be  one  upon  the  abdomen,  we  can,  with  advantage,  it 
would  appear,  and  upon  the  evidence  of  M.  Verneuil,  induce 
intestinal  evacuation.  These,  then,  are  clinical  facts  which  agree 
with  theoiy. 

There  are  cases  in  which  we  have  been  able  to  demonstrate 
that  the  grave  accidents  of  a  true  indigestion  were  of  a  toxic 
order.  Senator  has  seen  in  one  of  his  friends  a  fact  of  this  kind, 
— in  whom  intoxication  resulted  from  sulphuretted  hydrogen  pro- 
duced in  the  intestines  of  the  patient.  There  had  been  vomiting 
and  eructations,  giving  off,  as  well  as  the  gases  emitted  by  the 
anus,  the  odor  of  rotten  eggs.  The  symptoms  consisted  of 
fainting,  anxiety,  and  clouding  of  the  intellect.  But  the  poison 
could  be  detected  in  the  emunctories ;  the  emitted  gases  black- 


INTESTINAL  AUTO-INTOXICATION.  149 

ened  paper  impregnated  with  acetate  of  lead  ;  the  stools,  the 
urine  also,  contained  sulphuretted  hydrogen.  We  could,  there- 
fore, notice  in  these  cases  certain  symptoms  which  contribute  in 
part  to  the  classical  picture  of  poisoning  by  H2S,  as  in  certain 
dyspepsias.  We  have  demonstrated  the  presence  of  this  poison 
in  the  intestines,  and  then  in  the  urine ;  it  is,  therefore,  certain 
that  it  had  traversed  the  blood. 

In  some  people  special  foods,  without  being  either  toxic  or 
putrid,  induce  regularly  an  indigestion  and  grave  phenomena. 
In  similar  cases,  if  there  is  intoxication,  it  is  the  result  not  of 
the  food,  but  of  the  non-digestion  ;  the  digestive  juices  cease  to 
transform  food  which  the  stomach  does  not  care  to  receive  ; 
the  nervous  system  produces  disorders  of  secretion  ;  the  gastric 
juice  stops  flowing  into  the  stomach,  or  else  the  HC1  is  absent 
from  it  at  the  moment  of  the  conflict  of  the  food  with  the 
microbes.  But  the  HC1  not  only  serves  the  purpose  of  swelling 
and  of  l)3'drating  the  alimentary  mass,  it  ought  to  protect  it 
against  parasitic  ferments.  These  being  no  longer-  neutralized, 
anomalous  fermentations  are  produced  in  the  stomach  and  in 
the  intestines ;  the  toxic  products  of  these  fermentations  are  re- 
absorbed.  There  arises  from  this  an  intoxication,  which  is  not 
serious,  fortunately,  because  the  renal  function  protects  the 
organism. 

In  1882  I  made  known  the  following  observation:  A  man 
could  not  take  fish,  cooked  the  day  before  and  eaten  cold.  One 
day,  when  he  had  partaken  of  this,  which  his  nervous  system  did 
not  accept,  digestion  was  arrested,  and  he  experienced  the 
ordinary  symptoms  of  an  indigestion,  at  first  stomachal  and 
then  intestinal.  Diarrhoea  Listed  not  only  until  the  last  particles 
of  the  ingested  food  were  eliminated,  but  well  beyond  that  even. 
It  was  accompanied  by  prostration  and  anguish.  But  the  first 
accidents  only  appeared  after  a  veritable  incubation  of  eight 
hours,  during  which,  without  doubt,  microbes  had  formed  the 
amount  of  poison  which  caused  so  prolonged  an  intoxication; 
and,  in  order  that  there  should  be  formed  such  an  abundance  of 
the  poison,  it  was  necessary  that  there  should  have  been  an 
undoubted  multiplication  of  normal  bacteria  in  the  digestive 
canal.  In  fact,  I  have  been  able  to  estimate  the  quantity  of 


150  LECTURES   ON   AUTO-INTOXICATION. 

microbes,  in  these  cases,  as  one-third  of  the  faecal  mass.  There 
was  an  increase  of  the  intestinal  alkaloids,  since  from  12  grammes 
of  faecal  matter  I  was  able  to  remove  sufficient  alkaloids  to  esti- 
mate the  proportion  of  it  as  15  milligrammes  per  kilogramme 
of  faecal  matter.  In  the  urine  was  also  found  a  quantity  of 
alkaloids  fifty  times  greater  than  the  normal  amount. 

That  is  a  case,  therefore,  in  which,  without  there  having  been 
an  introduction  of  meat  in  a  state  of  fermentation  into  the 
digestive  canal,  and  without  our  being  able  to  establish  particular 
microbes,  there  was  produced,  by  the  multiplication  alone  of 
normal  bacteria,  a  considerable  increase  of  one,  at  least,  of  the 
toxic  substances  which  the  intestine  ordinarily  receives.  I  know 
of  the  circumstance  of  three  people  who  were  simultaneously 
seized  by  accidents  of  the  same  kind.  Breakfasting  together, 
they  had  eaten  fish,  with  a  certain  distaste,  about  10  or  11  in 
the  forenoon.  At  7  o'clock  at  night  one  of  the  three  felt  indis- 
posed ;  the  other  two  sat  down  at  table,  but  found  themselves 
attacked,  at  the  time  of  dessert,  by  identical  symptoms.  It  was 
a  question  of  an  illness  consisting  of  vertigo,  prostration, 
vomiting,  and  diarrhoea.  These  symptoms  were  not  the  result 
of  an  intoxication,  since  they  only  appeared  after  an  incubation 
of  eight  hours.  The  diarrhoea  was  not  that  which  supervenes  in 
indigestion  and  which  ceases  immediately  after  the  elimination 
of  food  not  digested  ;  it  continued,  night  and  day,  during  eight 
days,  with  from  eight  to  fifteen  evacuations  daity.  The  patients 
remained,  all  this  time,  in  a  semi-sleepy  condition.  The  three 
people  are  now  cured,  and  for  all  of  them  the  duration  of  the 
illness  was  the  same.  This  disease  might  be  attributed,  quite 
legitimately,  to  a  putrefaction  which  had  taken  place  in  the 
digestive  canal,  and  to  a  reproduction  of  putrid  agents  which 
had  formed  poisons. 

We  must  recognize  in  these  facts  something  analogous  to 
poisoning  by  sausages,  known  for  a  century  and  a  half,— since 
1735.  Facts  are  plentiful.  Muller,  in  1869,  had  collected  263 
observations.  Some  have  sought  for  the  toxic  material  in  the 
residue  of  meat.  This  research  had  remained,  without  any 
result,  until  Hoppe-Seyler  discovered  the  existence  of  an  al- 
kaloid, but  without  demonstrating  its  toxicity.  Brouarclel  and 


TAINTED   MEATS   AND   SAUSAGES.  151 

Botmy,  more  fortunate,  have  demonstrated  the  toxicity  of  an 
alkaloid  which  was  contained  both  in  the  viscera  of  a  woman 
who  died,  after  having  eaten  some  preserved  goose,  and  in  what 
was  left  of  this  goose.  This  alkaloid  presented  analogies  with 
conicine,  but  also  differences. 

It  is  certain  that  true  intoxication  may  result  from  the  eating 
of  tainted  meats.  Gaspard  and  Panum  have  shown  that  the 
putrefaction  of  meat  develops  a  poison  capable  of  inducing 
accidents  both  serious  and  fatal.  But  in  these  cases  the  symp- 
toms are  quickly  developed;  thej?  commence  half  an  hour  after 
the  ingestion  of  tainted  meat.  Besides,  in  a  general  wajr,  we 
do  not  eat  meat  actually  putrefied  and  alreadj7'  capable  of  intoxi- 
cating by  itself.  We  ingest  meat  which  is  only  beginning  to 
putrefy,  in  the  depths  of  which  microbes  are  at  work  determin- 
ing a  fermentative  process,  which  goes  on,  under  conditions  par- 
ticularly favorable,  when  the  tainted  food  has  found  its  way  into 
the  digestive  tube.  The  accidents  which  result  from  it  are 
slowly  developed  ;  they  only  light  up  eight  to  eighteen  hours 
after  the  ingestion  of  suspected  foods.  In  this  period  of  incu- 
bation no  sj'mptom  reveals  the  explosion  which  is  preparing; 
but,  once  the  poison  is  formed,  toxic  accidents  are  quickly 
developed. 

Krautzer  has  related  a  case  of  intoxication  by  sausages. 
Four  people  had  treated  themselves  to  Wtirtemberg  sausages 
scarcely  sufficiently  cooked,  for  people  with  delicate  tastes 
prefer  particularly  sausages  the  superficial  part  of  which  alone 
has  been  influenced  by  the  fire.  Out  of  these  four  people,  one 
remained  free  from  any  symptom,  the  other  three  were  taken  ill, 
and  one  of  them  died.  After  an  incubation  period  of  eighteen 
hours,  the  symptoms  experienced  were  almost  identical  in  in- 
tensity ;  they  consisted  in  disturbances  of  sight — strabismus, 
diplopia,  ptosis,  pupillary  dilatation — and  paralytic  phenomena. 
Injections  of  pilocarpine  which  were  made  did  not  induce  perspira- 
tion. Thus,  there  is  a  form  of  intoxication  caused  by  a  poison 
which  dilates  the  pupil  and  hinders  the  secretion  of  sweat,  which, 
consequently,  is  not  awanting  in  analogy  to  atropine.  And  yet, 
amongst  the  putrid  alkaloids,  there  is  one  which  is  endowed  with 
analogous  properties,  which  I  had  formerly  extracted  from  the 


152  LECTURES   ON   AUTO-INTOXICATION. 

faecal  matter  of  patients  the  subjects  of  typhoid  fever, — a  disease 
in  the  course  of  which  intestinal  putrefactions  are  very  intense. 

We  have  just  witnessed  a  small  epidemic  in  a  family.  We 
have  also  seen  epidemics  of  a  similar  nature  visit  with  severity 
a  whole  locality.  The  unwholesome  flesh  of  an  animal  is  given 
out  for  consumption  in  a  village,  at  the  time  of  a  fete,  which 
draws  a  great  many  people  there.  The  incubation  of  accidents 
having  been  long  amongst  the  first  consumers,  the  tainted  meat 
continues  to  be  distributed  amongst  the  people  who  have  come 
from  neighboring  villages.  These,  returned  each  to  his  own 
house,  are  seized  with  identical  troubles,  and  quite  a  series  of 
small  epidemics  is  developed,  having  for  its  origin  the  infection 
caused  by  the  unwholesome  meat  consumed  in  the  village  where 
the  fete  had  taken  place. 

Twelve  years  ago  I  broke  the  lance  with  Lebert  in  the  inter- 
pretation of  the  epidemic  at  Andelfingen.  In  the  little  town  in 
Switzerland,  a  large  number  of  deaths  resulted  from  an  intoxi- 
cation due  to  diseased  meat.  And  yet  there  was  always  a  slow 
incubation  and  a  long  duration,  which  eliminated  the  idea  of 
intoxication.  There  was  question  rather  of  a  disease  which  de- 
veloped gradually  in  the  individual,  and  continued  after  the  com- 
plete elimination  of  the  tainted  food.  In  similar  cases  the  sub- 
stances— although  healthy — after  ingestion  putrefied  in  their  turn. 

Some  have  thought  that  this  disease  was  trichinosis  or  typhoid 
fever.  Griesinger  was  party  to  this  last  opinion.  Lebert,  on  the 
contrary,  was  inclined  to  regard  it  as  an  intoxication  from  tainted 
meat.  Having  had  the  documents  in  hand,  I  insist  upon  the  long 
duration  of  the  incubation  which  was  observed  in  the  patients. 
It  has  been  shown  since  that  there  could  not  be  any  question  of 
trichinosis.  At  the  autopsy  of  some  of  the  people  who  had 
been  at  that  time  ill,  and  had  recovered,  made  a  long  time  after- 
ward, no  calcified  cysts  were  found  in  their  muscles.  If  one 
allies  himself  with  the  opinion  of  Lebert,  he  can  only  accept  the 
unwholesome  meat  as  having  caused  the  intoxications;  the 
accidents  can  only  be  explained  by  the  mechanism  of  infection. 
Why  had  certain  individuals  no  sign  of  illness,  in  spite  of  the 
fact  that  they  consumed  the  same  meat  as  those  who  became  ill 
or  died?  It  is  probable  that  they  had  eaten  the  parts  of  the 


AUTO-INTOXICATION    AND  INFECTION.  153 

tainted  meat  that  were  the  best  cooked, — the  external  parts, — 
where  the  action  of  heat  had  in  part  neutralized  the  poison. 

Thus,  in  the  famity  epidemic  of  which  I  have  just  spoken, 
out  of  four  people  who  ate  the  same  sausage,  one  remained  free 
from  accident.  This  fortunate  individual  was  the  apprentice,  and 
to  whom  the  masters  had  given  the  crust  of  the  sausage, — a  part 
much  less  prized  by  them  than  the  central,  but  in  which  microbes 
must  have  been  destroyed  by  the  action  of  heat.  The  infection 
in  the  cases  which  I  have  just  examined  is  not  an  infection  with- 
out any  relation  to  intoxication,  for  there  is  no  question  of  a 
general  infection,  but  of  a  surface  infection.  Without  doubt, 
there  is  at  once  induced  an  increase,  more  or  less  rapid  and 
enormous,  of  the  quantity  of  infectious  agents  introduced  into 
the  digestive  canal ;  but,  secondaril}'  to  infection,  there  is,  in  all 
probability,  produced  an  intoxication.  There  are  infectious 
maladies  in  which  microbes  inhabit  the  blood  ;  they  can  subtract 
oxj'gen  from  the  blood-cells  or  from  emboli  in  the  small  vessels. 
There  are  other  infectious  diseases  where  microbes  are  present 
in  certain  tissues,  and  induce  therein  anatomical  lesions.  In  all 
these  cases  the  symptoms  and  death  are  easily  explained.  But 
there  are  other  infectious  diseases  where  microbes,,  only  exist 
upon  a  mucous  surface,  where  they  do  not  penetrate,  and  do 
not  alter  the  limiting  membrane.  How,  in  these  cases  of  sur- 
face infection,  are  we  to  explain  the  general  symptoms  and 
death,  if  it  be  not  by  intoxication  ?  The  danger  as  regards  the 
organism  can  only  arise  from  the  absorption  b}'  it  of  the  toxic 
products  secreted  by  the  infectious  agents.  The  small  microbes 
form  poisons  like  many  large  mushrooms. 

There  are  cases  in  which  infection  no  longer  operates  in  an 
acute  transitory  manner,  but  during  several  months  and  years; 
it  is  the  result  of  habitual  putrefactions,  of  which  the  digestive 
tube  is  the  seat,  in  many  of  the  chronic  diseases  which  affect  it, 
and  which  are  opposed  alike  to  good  digestion  as  to  the  healthy 
elaboration  of  material.  This  is  seen  in  cancer  of  the  stomach, 
in  certain  chronic  dyspepsias,  and  in  dilatation  of  the  stomach. 
Thus,  besides  the  inconveniences  which,  from  a  nutrition  point 
of  view,  flow  from  imperfect  digestion  and  insufficient  alimenta- 
tion, we  see  symptoms  and  alterations  arise  which  bear  witness 
to  the  chronic  deterioration  of  the  organism  by  intoxication. 


LECTURE   XVIII. 

CHRONIC  G ASTRO-INTESTINAL  AUTO-INTOXICATIONS — DILATATION 
OP  THE  STOMACH. 

Chronic  auto-intoxication,  having  as  the  point  of  its  origin  the  digestive  canal,  is 
observed  in  chronic  diarrhoea,  cancer  of  the  stomach  or  of  the  intestine,  and 
in  chronic  dyspepsia.  Dilatation  of  the  stomach  may  be  taken  as  the  type  of 

the  morbid  states  which  produce  chronic  auto-intoxication. Incredulity 

of  a  part  of  the  medical  public  as  regards  the  subject  of  dilatation  of  the 
stomach.  Its  frequency  demonstrated  by  clinical  statistics.  Why  it  lias 
been  until  pow  unknown.  It  can  only  be  revealed  by  physical  signs.  Insuf- 
ficiency of  percussion  as  the  means  of  diagnosis  of  dilatation.  Value  of  the 

splashing  sound  as  a  means  of  delimitation  of  the  stomach. Consequences 

of  gastric  dilatation. Direct  symptoms  on  the  side  of  the  gastric  tube  and 

its  annexes.  Gastritis.  Gastro-intestinal  dyspepsia.  Hepatic  congestion. 
Ectopia  of  the  right  kidney  :  floating  or  mobile  kidney  only  exists  in  women 
and  military  men  ;  it  is  induced  by  repeated  congestion  of  the  liver  in  people 
the  base  of  whose  chest  is  made  to  undergo  habitual  constriction. Acci- 
dents remote  and  at  a  distance.  Disorders  of  innervation  :  sensibility  to 
cold.  Disorders  of  the  senses  and  intelligence.  Disorders  of  general  nutri- 
tion and  of  the  emunctories.  Skin  affections.  Catarrh  of  mucous  mem- 
branes. Albuminuria  and  peptonuria.  Inflammation  of  certain  tissues  and 

of   phlebitis. Alterations    of   the    osseous    tissues :    deformity    of    the 

phalango-phalangeal  articulations  of  the  fingers.  Its  semeiological  value; 
possible  relation  between  dilatation  of  the  stomach,  rachitis,  and  osteomala- 

cia. How  can  we  explain  the  reaction  of  dilatation  of  the  stomach  upon 

the  whole  of  the  organism  ?  Beau  had  already  taught  how  dyspepsias  pro- 
duce an  impression  upon  the  nervous  system.  .Dyspeptic  coma. General 

accidents  of  dilatation  of  the  stomach  are  no  more  surprising  than  those  of 
nephritis.  Functional  dignity  and  importance  of  the  digestive  canal  in  the 
relative  positions  of  the  organs.  Why  the  train  of  symptoms  in  dilatation 
of  the  stomach  should  not  be  confounded  with  arthritism ;  it  constitutes,  at 

the  most,  minor  arthritis. Clinical  types  of  dilatation  of  the  stomach: 

latent  forms,  dyspeptic,  hepatic,  neurotic,  cardiac,  asthmatic,  renal,  cutane- 
ous, rheumatic,  acute  or  chronic  consumptive. — -Diseases  of  debility  in- 

which  dilatation  of  the  stomach   is  induced  :  chlorosis,  tuberculosis. 

Dilatation  of  the  stomach  is  the  result  of  an  acquired  diathesis. 

THE  facts  enumerated  in  the  preceding  lecture  do  not  all 

constitute  a  strict   demonstration   of  intoxication, — they  onl}' 

cause  it  to  be  presumed.     Nevertheless,  there  are  some  of  them 

which  cany  conviction, — that  of  Senator,  for  example,  in  which 

(154) 


TOXINS   OP   INTESTINAL   ORIGIN.  155 

one  poison  only — sulphuretted  hj'drogen — was  found  in  the 
intestine  and  in  all  the  excreted  products  :  that  which  is  personal 
to  me,  and  in  which  I  have  found  alkaloids  in  enormous  quan- 
tity in  the  urine,  as  well  as  in  the  intestine. 

Secondary  intoxication  can  alone  explain  the  fatal  accidents 
consecutive  to  surface  infection ;  for,  if  we  understand  the 
mechanism  of  death  in  diseases  where  the  infectious  agent  is 
spread  out  in  the  whole  of  the  organism,  in  the  blood,  or  in  the 
principal  viscera,  how  could  life  be  arrested  by  a  disease  in 
which  the  infectious  agent  rests  on  the  surface  of  the  mucous 
membrane  of  the  digestive  tube,  if  that  infectious  agent  does 
not  forniva  poison  which,  being  absorbed,  diffuses  itself  through 
the  whole  economy  so  as  to  impregnate  the  cellular  elements  or 
to  energetically  impress  the  nervous  system  ? 

There  are,  besides,  cases  in  which  some  have  been  able  to 
isolate  and  define  chemically  toxic  bodies ;  Brouardel  and 
Boutin}7  have  done  so.  There  are  others  where  the  symptoms 
observed  bear  a  remarkable  analogy  to  certain  well-known  forms 
of  poisoning.  Lepine  and  Daniel  Molliere  saw  a  case  of  intes- 
tinal obstruction  followed  \>y  accidents  simulating  intoxication 
by  atropine,  with  scarlatinal  redness,  mydriaSM,  and  acceleration 
of  the  pulse. 

We  are  now  going  to  approach  chronic  intoxications  having 
as  their  point  of  origin  the  intestinal  tube.  They  may  be  ob- 
served in  chronic  diarrhea,  in  cancer  of  the  stomach  or  intestine, 
in  chronic  dyspepsia, and,  above  all,  in  dilatation  of  the  stomach. 

A  year  ago,  I  brought  forward  the  statistical  analysis  of  220 
cases  of  dilatation  of  the  stomach  which  I  had  personally  ob- 
served. I  could  bring  forward  to-day  nearly  400  cases,  of  which 
274  have  been  seen  by  me  outside  of  the  hospital,  and  the  others 
in  my  service.  When  I  announced  to  3-011,  last  year,  my  virws 
upon  the  consequences  of  dilatation  of  the  stomach,  I  had  not 
met  opponents  by  word  alone.  But  at  the  Medical  Societ}*  of 
the  Hospitals,  in  the  press,  and  in  conversations  with  confreres, 
I  have  found  incredulity  and  jesting,  which  in  our  country 
always  welcome  a  new  announcement.  I  believe  that  my  oppo- 
nents have  passed  bej'ond  the  question  ;  that  they  cannot  judge 
otherwise,  because  they  were  in  want  of  facts  to  control  my 


156  LECTURES   ON   AUTO-INTOXICATION. 

way  of  viewing  it.  I  do  not  know  whether  my  opponents  have 
subsequently  made  the  control  Of  that  which  I  had  advanced ; 
but  I  have  done  it.  Some  may  sa}',  it  is  true,  that  my  control 
ought  to  be  held  only  as  a  suspicion.  And  yet,  if  I  am  not  mis- 
taken, it  seems  to  me  that  the  denials,  which  were  universal,  are 
fewer  and  less  noisy ;  they  may  carry  with  them  divergence  of 
opinion  as  to  the  frequency  of  such  a  fatal  concomitant,  or  bf 
disease  itself,  but  people  no  longer  deny  the  existence  of  it. 

I  have  said  that  dilatation  of  the  stomach  was  neither  an 
anatomical  curiosity  nor  a  rarity  ;  that,  whilst  very  frequent  in 
the  sick,  it  is  relatively  uncommon  in  the  healthy;  and  I  have 
mj^self  asked  the  question  whether  people  who,  in  appearance, 
are  not  ill,  but  still  have  the  physical  signs  of  dilatation  of  the 
stomach,  are  truly  healthy?  I  have  said  that,  generally  speak- 
ing, gastric  dilatation  had  existed  for  a  long  time  before  the' 
commencement  of  the  disease  with  which  we  find  it  associated, 
and  that  there  is  a  cause  for  considering,  in  a  very  large  number 
of  patients,  besides  the  principal  disease  by  which  they  are 
designated,  the  other,  dilatation  of  the  stomach,  which  has  the 
appearance  of  being  an  accessory,  and  which  has,  perhaps,  pre- 
pared the  way  for  invasion  of  the  first. 

Why  has  dilatation  of  the  stomach  been  so  little  known  for 
such  along  time  past,  and  yet  so  frequent?  Because  it  cannot 
be  recognized  save  by  establishing  its  physical  signs  ;  but  often- 
est,  on  examination  of  the  patient,  the  symptoms  of  which  they 
complain  are  not  of  the  nature*to  lead  us  to  search  for  it. 

Indeed,  I  can  affirm,  from  an  analysis  of  the  facts,  that 
dilatation  of  the  stomach  may  exist  without  inducing  anomalous 
sensations,  without  dyspeptic  or  gastralgie  symptoms,  in  two- 
thirds  of  the  cases.  It  is  a  disease  which  does  not  announce 
itself;  we  know  that  it  passes  unperceived. 

The  physical  signs  which  permit  of  the  recognition  of  dila- 
tation of  the  stomach  can  be  furnished  by  different  methods  of 
clinical  examination.  Percussion  is  difficult  and  delicate  to 
practice,  sometimes  insufficient,  and  is  rendered  false  in  its 
results,  owing  to  tympanites  of  the  colon.  Succussion  furnishes 
no  certain  sign;  it  may  bring  out  the  noise  of  fluid  in  a  normal 
stomach,  and  yet  it  cannot  reveal  the  extent  of  the  dilatation. 


DILATED   STOMACH   AND   ITS   DETECTION.  15 f 

I  Lave  pointed  out  as  the  best  sign  the  sound  of  splashing, 
already  drawn  attention  to  by  Chomel.  But  it  is  necessary,  in 
order  that  it  should  have  the  whole  of  its  semeiotic  value,  that 
there  should  not  have  been  recently  the  ingestion  of  any  con- 
siderable quantity  of  food  capable  of  producing  mechanically  a 
fleeting  distension ;  it  is  necessary  that  splashing  should  be 
detected  in  a  person  who  is  fasting.  If  3-011  do  not  hear  it  at 
the  first  stroke,  3rou  must  not  affirm  that  the  stomach  is  not 
dilated.  It  may  be  flattened  and  fall  flabbily  behind  the  abdom- 
inal wall,  like  an  apron  ;  but  if  you  introduce  one-third  of  a 
glass  of  water  into  a  dilated  stomach,  you  will  immediately  hear 
splashing  over  a  region  much  greater  in  extent  than  in  the 
normal  state.  In  the  healthy  man  this  phenomenon  is  never 
perceptible  fifteen  hours  after  a  meal.  I  still  admit,  through 
courtesy,  that  it  is  necessary  to  perceive  the  splashing  below  the 
middle  of  a  line  drawn  from  the  umbilicus  to  the  point  nearest 
to  the  border  of  the  left  costal  arch.  But,  in  reality,  this  line  is 
of  little  importance.  Every  stomach  which  is  not  retracted 
when  it  is  empty  is  a  dilated  stomach.  Dilatation  is  not  disten- 
sion. A  dilated  stomach  is  a  stretched  stomach  the  cavity  of 
which  is  apparent  only  when  it  is  empty,  because,  though  its 
walls  then  touch  each  other,  it  is  no  longer  capable  of  diminishing 
its  own  size  by  retraction. 

It  is  not  enough  to  know  only  that  the  stomach  is  dilated  ;  it 
is  necessary  to  know,  in  a  precise  manner,  the  dimensions  of 
this  dilated  stomach,  to  know  its  extreme  limit  below  and  its 
extreme  limit  to  the  right  of  the  median  line,  to  pursue  the 
search  after  splashing  until  it  disappears  from  above  downward 
and  from  left  to  right,  and  to  establish  thus  its  limits  by  the 
determination  of  the  two  lines,  traced  upon  the  limits  of  the 
zone  where  we  observe  splashing, — one  of  these  lines  being 
horizontal,  the  other  vertical,  parallel  to  the  median  line  and 
situated  to  the  right  of  this  line. 

Is  it  possible,  as  some  have  said,  to  confound  stomachal  with 
intestinal  splashing?  No;  this  is  heard  lower  down.  Besides, 
we  proceed  to  seek  it  from  above  downward,  and  from  left  to 
right.  In  addition,  it  is  easy  to  establish  that  the  arrival  of 
water  in  the  stomach  is  immediately  followed  by  the  noise 


158  LECTURES   ON    AUTO-INTOXICATION. 

(bruit)  of  splashing ;  water  has  not  had  sufficient  time  to  reach 
the  colon.  I  still  insist  upon  the  necessity  of  assuring  one's  self 
of  the  constancy  of  the  phenomenon,  which,  sought  for  under 
the  same  conditions,  ought  always  to  be  perceived  at  the  same 
points. 

If  the  demonstration  can  be  considered  as  clinically  accom- 
plished, it  is  also  anatomically.  We  can  cause  chopping  to 
appear  in  the  cadaver,  and  we  delimit  the  dimensions  of  the 
area  where  it  is  heard  ;  we  open  the  abdominal  wall,  and  we  can 
convince  ourselves  that  these  are  indeed  the  limits  of  the 
stomach  ;  afterward,  we  sew  up  the  wall,  and  anew  we  observe 
chopping  within  the  same  limits. 

Be  certain  that  we  do  not  often  give  ourselves  the  trouble  of 
seeking  for  dilatation  of  the  stomach  in  the  exact  conditions 
which  I  have  indicated,  and  still  less  of  measuring  it.  Yet  we 
ought  to  be  able  to  know  exactly  the  number  of  centimetres 
which  a  stomach  measures.  If  there  truly  exist  marked  dilata- 
tion of  the  stomach,  such  as  I  have  indicated;  if  there  are 
stomachs  which,  during  several  years,  reach  almost  to  the  pubis, 
as  we  have  been  able  to  verify  them  at  the  autopsy,  it  appears 
a  priori  impossible  that  such  an  anomaly  could  exist  without 
disturbance  of  health.  Assuredly,  one  can  have  a  large  stomach 
and  not  experience  dyspeptic  troubles,  but  he  is  the  victim  of 
disturbances  in  the  elaboration  of  food.  Men  whose  stomach 
is  dilated  complain  of  their  indisposition  as  being  of  very  slow 
development ;  they  are,  nevertheless,  ill  for  a  long  time  before 
becoming  patients.  Their  diseases  are,  therefore,  diseases  of 
debility,  because  the  alimentary  material,  incompletely  digested 
and  undergoing  putrid  fermentation,  is  no  longer  sufficient  for 
their  nutrition.  They  are  the  victims  of  an  insufficient  alimenta- 
tion both  because  the  imperfection  of  digestion  reduces  the 
value  of  assimilable  material  and  because  putrid  fermentation 
destroys  another  part  of  this ;  for  the  hydrochloric  acid  of  the 
gastric  juice,  being  too  diluted,  is  no  longer  capable  of  oft'ering 
opposition  to  the  anomalous  fermentative  actions  induced  by 
the  figured  ferments. 

We  notice,  then,  in  individuals  who  present  the  physical  signs 
of  dilatation  of  the  stomach :  1.  Pulmonary  phthisis.  2.  Chlorosis 


SYMPTOMS   OF   DILATED   STOMACH.  159 

(both  of  which  accompany  gastric  dilatation, — the  first  in  two- 
thirds  of  the  cases,  the  second  in  four-fifths).  3.  Nervous  or  hypo- 
chondriac S3rtnptoins.  We  see  men  without  energy,  who  present 
themselves  at  the  hospital  because  they  can  no  longer  work,  on 
account  of  phjrsieal  and  mental  debility  ;  we  regard  them  often 
as  idlers,  if  not  as  hypochondriacs;  we  make  an  error  in  diag- 
nosis. 4.  Lastly,  other  symptoms,  so  varied  and  so  numerous 
that  their  mention  at  first  provokes  incredulity. 

I  shall  not  return  to  the  details  which  I  gave  last  }-ear  upon 
this  subject.  I  ought,  nevertheless,  to  make  again  a  brief  men- 
tion of  them.  We  meet,  amongst  patients  whose  stomach  is 
dilated,  symptoms  directly  connected  with  the  digestive  tube. 
The  appetite  is  in  general  preserved ;  it  may  be  augmented.  The 
most  of  those  who  are  the  subjects  of  dilatation  eat  largely. 
Ingestiou  is  not  at  all  painful.  But,  at  the  end  of  two,  three,  or 
four  hours,  the  stomach  is  blown  out,  eructations  are  produced, 
inodorous  at  first,  then  musty,  sometimes  fetid  ;  a  sensation  of 
heaviness  or  of  heat  at  the  epigastrium  ;  pyrosis  ;  regurgitations, 
whose  acid  odor  demonstrates  the  reality  of  the  anomalous  fer- 
mentations which  are  going  on  in  the  stomach,  for  the  hydro- 
chloric acid  has  no  acid  odor.  This  is  due  to  acetic  acid.  The 
faeces  are  generally  doughy,  stinking,  acid  ;  although  soft,  they 
are  expelled  slowly,  and  with  pain.  Their  acidity  is  due,  we 
can  assure  ourselves,  to  the  predominance  of  acetic  acid. 

The  consequence  of  this  development  of  acid  in  the  whole- 
length  of  the  digestive  tube  is  an  inflammatory  condition.  We 
notice  catarrh  of  the  stomach,  ulcerative  gastritis,  to  which 
patients  often  succumb  after  twentj'-five  years  of  bad  stomach  ; 
these  are  the  false  cancers,  as  they  are  called,  or  malignant  gas- 
tritis without  tumor.  The  large  intestine  is  inflamed ;  around 
the  Hecal  matter  are  seen  glairy  secretions  and  sometimes  blood 
(membranous  enteritis). 

Besides  the  phenomena  of  gastro-intestinal  dyspepsia,  there 
exists  hepatic  congestion.  We  find,  amongst  people  with  dil:iU-d 
stomach,  a  swollen  liver,  often  indolent;  sometimes  there  exi>ts 
an  aching  in  the  right  hypochomlriuin ;  sometimes  jaundice, 
without  colorless  stools.  This  congestion  of  the  liver  is  of 
short  duration,  and  is  modified  vi-ry  rapidly  ;  it  may  appear  and 


160  LECTURES   ON   AUTO-INTOXICATION. 

disappear  in  two  or  three  days ;  it  sometimes,  too,  passes  unno- 
ticed. Of  the  274  cases  which  I  have  observed  outside  the 
hospital,  I  have  found  it  thirteen  times  in  100 ;  that  is  to  say,  in 
one-eighth  of  the  cases. 

The  knowledge  of  this  tendency  to  hepatic  congestion  is 
not  without  interest,  from  the  point  of  view  of  the  explanation 
of  the  recurring  jaundice  of  infants.  It  also  explains,  perhaps, 
the  ectopia  of  the  right  kidney,  which  I  have  always  seen  co- 
incide with  a  dilatation  of  the  stomach,  but  I  can  only  believe 
that  this  coincidence  is  accidental.  It  was  made,  in  1875,  by 
Bartels.  This  observer  has  an  opinion  different  from  mine  as  to 
the  bond  which  unites  these  two  facts, — ectopia  of  the  kidney 
and  dilatation  of  the  stomach.  Bartels  believes  in  the  primary 
displacement  of  the  kidney.  The  kidney,  says  he,  falls  upon  the 
horizontal  portal  portion  of  the  duodenum  and  opposes  mechani- 
cally the  departure  of  food  from  the  stomach,  which  thus 
dilates.  But  if  the  kidney  is  displaced  primarily,  why  is  it 
always  the  right  kidney  ?  I  say  that  the  right  kidney  is 
dislocated,  because  it  is  the  liver  which  pushes  it  out  of  its 
place.  We  do  not  find  ectopia  of  the  right  kidne}'  in  all  people 
whose  stomach  is  dilated,  but  only  in  those  whose  thorax  is  the 
seat  of  a  habitual  constriction  at  its  base,  in  women  and  military 
men.  Bartels  has  recognized  this  fact.  The  corset  and  the 
abdominal  band  prevent  the  liver,  when  it  increases  in  volume, 
from  passing  in  front  of  the  kidney.  Thus,  if,  ten  or  fifteen 
times  a  year,  there  are  produced  sudden  developments  of  hepatic 
congestion,  we  can  easily  understand  how  the  kidney,  pressed 
against,  little  by  little,  is  displaced  consecutively  to  the  gradual 
elongation  of  its  vascular  attachments.  We  observe,  in  all  the 
cases  of  dilatation  of  the  stomach,  luxation  of  the  kidney  four- 
teen times  out  of  100.  If  we  consider  sex,  the  frequency  is  28 
per  cent,  in  women  and  3  per  cent,  only  in  men.  Thus,  if  in 
women  more  than  one-fourth  of  the  dilatations  are  attributable 
to  luxation  of  the  kidney,  dilatation  of  the  stomach  ought  to  be 
in  men  sensibly  less  frequent  than  in  women.  Yet  experience 
shows  that  dilatation  of  the  stomach  is  at  least  as  frequent  in 
men  as  in  women. 

Dilatation  of  the  stomach,  on  account  of  the  anomalous  fer- 


NERVOUS   SYMPTOMS   IN   DILATATION   OF   THE   STOMACII.        161 

mentations  which  are  the  consequence  of  it,  is  accompanied, 
besides,  by  distant  disturbances,  many  of  which  form  part  of  the 
classical  series  of  dyspepsias  and  are  considered  of  the  nature 
of  reflex.  These  are  first  the  nervous  symptoms  of  dyspeptics 
(dyspepsia  is  accompanied  by  dilatation  of  the  stomach  in  seven- 
eighths  of  the  cases). 

Those  who  are  ill  are  depressed  in  the  morning,  on  awaken- 
ing; at  the  end  of  half  an  hour  they  have  often  recovered  their 
alacrity.  They  complain  of  a  painful  circle  around  their  head, 
of  headache,  of  feeling  very  depressed,  an  uneasy  disposition ; 
sensibility  to  cold,  insomnia,  vertigo,  which  belong  to  the  history 
of  all  diseases  of  the  stomach ;  obscuration  of  sight,  hemiopia, 
diplopia,  weakness  of  the  right  internal  muscle  of  the  eye, 
hallucinations  of  sight ;  partial  and  fleeting  dropsy  of  the 
limbs, — of  an  arm  or  a  leg ;  contracture  of  the  extremities  of 
the  hands,  as  pointed  out  by  Kussmaul,  Dnjardin-Beaumetz, 
Hanot,  and  Hayem,  and  of  which  I  have  recently  met  with  an 
example.  I  have  seen  a  patient  who,  at  2  o'clock  in  the  morn- 
ing, awoke  in  a  start,  and  in  a  state  of  grief,  with  a  contrac- 
ture of  the  hands, — a  contracture  which  extended  up  to  the  arms 
and  the  shoulders ;  this  condition  lasted  for  five  weeks.  I  de- 
tected in  her  a  dilatation  of  the  stomach,  and  prescribed  the  ap- 
propriate treatment ;  on  the  following  night  she  had  not  the  crisis, 
nor  had  she  it  on  the  subsequent  evenings,  so  long  as  she  observed 
the  regimen.  One  day  she  failed  to  do  so  ;  the  same  evening  con- 
tracture of  the  hands  re-appeared.  It  has  entirely  disappeared 
since,  thanks  to  the  continued  observance  of  a  better  hygiene. 

I  have  noticed,  too,  transitory  aphasia,  and  once  fatal  syn- 
cope, disturbances  of  vascular  innervation,  a  sensation  as  if  two 
or  three  fingers  were  dead,  palpitation,  flushing  of  the  face  two 
or  three  hours  after  meals,  false  angina  of  the  breast,  nocturnal 
perspirations  (limited  to  the  head,  neck,  and  thorax).  I  would 
also  mention,  following  Chantemessc  and  Le  Noir,  bilateral  inter- 
costal neuralgia. 

All  these  phenomena  may  be,  strictly  speaking,  regarded  as 
reflex.  But  there  are  others  which  arise  from  the  abnormal 
metamorphosis  of  matter.  And,  as  for  these,  how  ara  they  to 
be  explained  if  not  by  intoxication  ? 

11 


162  LECTURES   ON   AUTO-INTOXICATION. 

Besides  the  nervous  symptoms  which  are  rightly  or  wrongly 
considered  reflex,  I  have  detected,  in  people  whose  stomach  is 
dilated,  symptoms  on  the  side  of  the  general  nutrition  and  dis- 
turbance of  the  emunctories. 

I  have  said  that  they  are,  in  general,  patients  who  are  chilly  ; 
they  have,  nevertheless,  free  perspirations,  night  and  day,  and 
after  the  least  exercise, — a  walk  on  foot  upon  even  ground,  or 
after  having  ascended  two  flights  of  stairs.  These  perspirations 
have  a  heavy  or  musty  odor,  as  of  mouldy  bread,  according  to 
the  statement  of  some  of  the  patients. 

We  notice  amongst  them  eczema  thirteen  times  out  of  one 
hundred,  pityriasis  in  front  of  the  sternum  or  of  the  head, 
pityriasis  versicolor. 

Urticaria  is  not  uncommon  amongst  those  suffering  from 
dilatation.  But  urticaria,  although  it  does  not  pass  for  a  dis- 
ease of  intoxication,  and  although  it  is  not  frequently  noticed 
in  the  course  of  infectious  diseases,  yet  it  has  arisen,  in  some 
unexplained  way,  during  indigestion  and  gastric  embarrassment. 
We  have  seen  it  follow  the  ingestion  of  mussels,  certain  stale 
fish,  and  various  shell-fish.  Are  not  these  all  toxic  causes  ?  Urti- 
caria has  often  been  observed  after  puncture  of  hydatid  cyst 
of  the  liver;  it  has  been  attributed,  in  similar  cases,  to  the  intro- 
duction of  a  part  of  the  fluid  of  the  cyst  into  the  peritoneum 
and  to  its  subsequent  entrance  into  the  lymphatic  channels ;  it 
would  be,  even  there,  a  kind  of  intoxication.  It  is  not  correct 
that  some  should  put  as  the  cause  of  it  exclusively  the  action  of 
the  peritoneum.  Whilst  chef  de  clinique,  I  have  seen  a  young 
girl,  the  subject  of  a  hydatid  cyst,  upon  whom  Behier  had  ad- 
vised a  large  opening  of  the  liver  to  be  made  by  means  of  suc- 
cessive cauterizations,  after  the  manner  of  Recamier  ;  in  order  to 
bring  about  adhesion  with  the  abdominal  wall,  he  had,  by  means 
of  Canquoin  paste,  produced  a  kind  of  tunnel  into  the  hepatic 
tissue.  He  reached  a  cyst  of  a  size  so  small  that  he  thought 
that  there  were  multiple  cysts  and  that  he  would  have  to  resort 
to  puncture,  to  be  made  in  the  depths  of  the  tunnel.  There 
only  flowed  out  a  few  spoonfuls  of  a  liquid  clearly  hydatid,  in 
which  booklets  were  detected  by  the  microscope.  He  pushes 
.the  treatment  farther,  and  there  is  seen  to  escape  a  jet  of  red 


SKIN    ERUPTIONS   AND   DILATATION   OP   THE    STOMACH.  163 

blood,  come  from  a  branch  of  the  portal  vein.  And  yet,  the 
only  accident  after  this  was  a  general  eruption  of  urticaria. 
It  is  evident  that  penetration  of  the  liquid  of  the  cyst,  took 
place- directly  into  the  blood,  and  that  there  was  here  clearly  a 
case  of  toxic  urticaria  without  any  intermeddling  of  the  peri- 
toneum. 

Besides,  I  think  that  urticaria  is  often  of  a  toxic  nature,  like 
other  congestive  eruptions  with  vesicles  on  the  skin  ;  quinine 
eruptions,  which  may  assume  the  erythematous  form  ;  scarlatinal 
or  papular,  like  a  variety  of  the  erythema  due  to  copaiva,  or 
like  the  exanthem  of  belladonna. 

Amongst  certain  young  girls,  we  see  acne  on  the  temples — on 
the  parts  about  the  chin — coincide  frequently  with  dilatation  of 
the  stomach,  as  well  as  acne  rosacea,  with  scarlet  redness  of  the 
nose  and  cheeks,  which  -develop  about  two  hours  after  meals, 
and  which,  for  a  long  time  past,  have  been  considered  as  indica- 
tions of  a  bad  stomach.  Are  not  these  cutaneous  manifestations 
of  toxic  origin,  like  those  which  often  follow  the  ingestion  of 
chloral ? 

I  suppose  that,  as  the  result  of  the  ingestion  of  these  various 
medicaments,  the  cutaneous  vasomotors  are  impressed  by  the 
direct  action  of  the  poison,  or  their  disturbance  is  the  result  of 
a  reflex  of  the  nervous  system.  Yet,  Avhen  it  is  a  question  of 
morbid  secretions,  like  acne  and  eczema,  it  is  difficult  to  admit 
the  interference  of  the  nervous  system.  Would  it  not  be  more 
advisable  to  incriminate  the  elimination  of  fatty  volatile  acids? 
Whatever  may  otherwise  be  the  interpretation,  the  empirical 
fact  of  the  linking  on  of  dilatation  of  the  stomach  to  a  large 
number  of  cutaneous  manifestations  remains  certain ;  it  is, 
therefore,  a  series  of  links  and  not  an  accidental  association. 
For  a  pathogenic  explanation  I  propose  to  you,  for  the  time 
being,  intoxication. 

The  mucous  membranes,  like  the  cutaneous  coverings,  serve 
for  the  elimination  of  gaseous  matters  and  volatile  fatty  acids 
arising  from  abnormal  fermentation  which  has  taken  place  in  the 
stomach.  The  odor  of  the  breath  is  a  witness  to  their  elimination 
by  the  respiratory  mucous  membrane.  Besides,  people  who  are 
the  subjects  of  dilatation  of  the  stomach  catch  cold  easily,  cougU 


164  LECTURES   ON    AUTO-INTOXICATION. 

habitually  ;  their  bronchi  secrete  mucous  sputa  which  are  with 
difficulty  detached,  and  lead  up  to  dyspnoea  and  rhouchi.  I 
have  (bund  sibilant,  noisy,  recurrent  bronchitis  ten  times  in 
every  one  hundred  of  my  actual  statistics  (instead  of  15  per  cent, 
in  my  statistics  of  last  year) ;  dyspnoeic  respiration  of  paroxysmal 
character,  recalling  the  advent  of  asthma,  four  or  five  times  in 
every  one  hundred.  I  have  also  noticed  recurring  coryza  and 
frequent  sneezing  in  the  morning.  These,  also,  I  suspect,  we 
must  rather  consider  the  result  of  the  elimination  of  toxic  sub- 
stances than  a  reflex  act. 

On  the  part  of  the  kidneys,  there  exist  important  disturb- 
ances. Without  speaking  of  ectopia,  upon  which  I  need  not  re- 
turn, and  whose  mechanism  is  quite  peculiar,  albumiuuria  is 
extremely  frequent,  not  only  as  a  trace,  but  in  measurably  large 
quantities,  in  the  form  of  a  retractile  coagulurn  when  the  action 
of  heat  is  made  to  follow  that  of  coagulating  reagents.  I  have 
established  it  seventeen  times  in  one  hundred  cases  in  my  most 
recent  statistics  (I  had  said  13  per  cent,  for  one  hundred  last 
year).  When  the  condition  of  the  stomach  has  been  relieved 
albuminuria  diminishes,  or  even  disappears,  to  return,  however, 
on  the  least  indiscretion  of  diet.  It  follows  in  a  line  parallel 
to  that  of  the  disease. 

Can  we  consider  the  albuminuria  as  dyscrasic  and  arising  from 
a  vitiation  of  the  general  nutrition  ?  Is  it  the  consequence  of  irri- 
tation, or  of  inflammation  of  the  renal  tissue  by  toxic  substances 
which  it  is  eliminating?  I  do  not  undertake  the  solution  of 
these  questions. 

Albuminuria  is  variable  as  regards  its  intensity  and  its  per- 
sistence ;  it  is  most  frequently  curable.  In  certain  cases  it  lasts 
for  a  long  time,  being  the  sign  of  a  renal  lesion.  M.  Tapret  had 
pointed  out  the  bruit  de  galop  in  a  case  in  which  albuminuria 
appeared  to  be  associated  with  the  existence  of  a  dilatation  of  the 
stomach  ;  the  albuminuria  having  disappeared,  the  heart  ceased  to 
beat  in  accordance  with  the  albuminuric  rhythm ;  later  on,  it  is 
true,  cardiac  troubles  had  returned.  I  have  observed  several 
analogous  cases. 

Peptonuria  is  frequent  in  dilatation ;  I  believe  I  was  the  first 
to  draw  attention  to  it.  Whilst  in  the  normal  state,  peptone 


AFFECTION    OF   TEIE   BOOT   TISSUES.  165 

cannot  be  discovered  in  the  blood,  either  because  it  has  been 
transformed  into  albumen  in  its  passage  through  the  walls  of  the 
intestine,  or  the  liver  has  changed  it,  or  the  white  blood-cells 
have  laid  hold  of  it.  In  certain  people,  the  subjects  of  dilated 
stomach,  it  passes  into  and  remains  in  the  blood,  and  is  dialyzed 
afterward  in  its  passage  through  the  kidneys. 

Let  us  now  put  upon  record  the  modifications  of  general 
nutrition  in  people  whose  stomach  is  dilated.  As  a  goodly 
number  of  the  organs  suffer,  it  is,  therefore,  not  surprising  that 
one  should  have  to  note  loss  of  power,  diminution  of  physical 
and  moral  energy,  emaciation  in  the  advanced  phases,  but  often, 
also,  lax  obesity  with  pallor,  abundant  deposit  of  unites  in  the 
urine,  increase  of  acidity  of  the  urine,  and  the  appearance  of  a 
red-wine  coloration  on  the  addition  of  perchloride  of  iron. 

Inflammation  may  seize  certain  of  the  tissues ;  we  notice 
phlebitis.  I  have,  twice  out  of  one  hundred  times,  noticed 
spontaneous  phlebitis,  and  I  have  insisted  upon  the  importance 
of  this  point,  which  no  longer  permits  us  to  accord  to  sponta- 
neous phlebitis  coming  on  in  the  course  of  a  chronic  d3rspepsia 
the  signification  which  Trousseau  assigned  to  it.  Purpura, 
which  indicates  fragilit}'  and  bad  nutrition  of  the  vessels,  is  met 
with  two  or  three  times  in  every  one  hundred. 

In  short,  I  ought  to  recall  the  existence  of  modifications  of 
the  bony  tissue  in  the  neighborhood  of  certain  articulations.  I 
have  insisted  upon  the  frequency  of  nodosities  on  the  phalan^o- 
phalangeal  articulations  of  the  fingers;  they  are  formed  by 
enlargement  of  the  bases  of  the  second  phalanx ;  in  some 
rare  cases  upon  the  anterior  part  of  the  base  are  seated  two 
lateral  nodules,  as  we  see  them  in  the  rheumatic  nodules  of 
Heberden,  which  are  always  found  at  the  third  articulation. 
We  often  see  the  four  fingers  of  the  two  hands  present,  simul- 
taneously, these  deformities.  Nearly  always  the  patients  are 
astonished  when  we  call  their  attention  to  these ;  the}'  consider 
that  they  have  always  had  them.  Sometimes,  however,  the 
parents  know  the  date,  approximately,  of  their  appearance,  after 
an  absence  from  home,  such  as,  for  instance,  their  return  from 
college.  In  some  people,  pains  are  felt  in  the  joints  which  have 
become  deformed. 


166  LECTURES   ON    AUTO-INTOXICATION. 

Sometimes  other  joints  may  be  deformed.  I  have  noticed,  at 
the  metacarpo-phaiangeal  articulation  of  the  thumb,  a  swelling  and 
pain.  In  cases  much  more  rare,  I  have  noticed  pain  and  swelling 
at  the  level  of  the  wrist;  we  sometimes  observe  painful  swellings 
of  other  joints,  and,  in  particular,  of  the  internal  extremity  of 
the  clavicle.  Out  of  the  whole  of  the  observations,  I  have 
noticed  joint  deformities  twenty-five  times  in  every  one  hundred, 
and  in  men,  taken  apart,  thirty-two,  times  in  one  hundred.  They 
are  susceptible  of  improvement,  or  of  lessening  if  the  stomach 
improve.  I  have  seen  oscillations  running  pai'allel  with  this 
condition. 

What  can  be  the  meaning  of  these  nodosities? 

Some  have  said,  in  opposition  to  me,  that  they  were  the  effect 
of  rheumatism,  just  as  dj'spepsia  is.  But,  really,  there  is  no 
choice  in  this  of  rheumatic  deformation.  Chronic  partial  rheu- 
matism affects  the  knee  and  the  hip  ;  the  nodosities  of  Heberden 
are  seated  at  the  third  articulation  of  the  fingers.  Asthenic 
primary  gout  and  deforming  rheumatism  seize  the  wrists  and 
the  phalango-phalangeal  articulations  at  once,  and  only  sec- 
ondarily the  second  articulations.  Why  do  we  not  see,  in 
dilatation  of  the  stomach,  other  joints  seized, — the  knees  and 
metacarpo-phaiangeal?  Otherwise,  the  subarticular  signs  of 
rheumatism  are  awanting  in  those  who,  having  dilatation  of  the 
stomach,  are,  at  the  same  time,  the  bearers  of  nodosities  on  the 
fingers ;  it  is  only  by  a  begging  of  the  question  that  we  attribute 
them  to  arthritism. 

In  any  case,  I  maintain  the  reality  of  the  following  empirical 
fact :  When  you  find  people  whose  fingers  present,  at  the  level 
of  the  second  articulation,  the  nodosities  of  which  I  have  spoken, 
you  will  nearly  always  notice  in  them  the  physical  signs  of  dil- 
atation of  the  stomach. 

We  may  see  nodosities  situated  also  at  the  second  joint  of  tlie 
big  toes ;  one  is  rarely  led  to  seek  for  them  in  consultation,  but, 
seeking  them,  I  have  found  them  in  some  cases. 

Not  only  may  other  joints  be  affected,  but  the  osseous  tissue 
itself  may  suffer,  even  in  the  continuity  of  the  long  bones.  Thus 
may  sometimes  be  explained  rachitis  and  osteomalacia.  If  in  the 
child,  rachitis,  as  M.  Comby  has  said,  may  be  one  of  the  con- 


DYSPEPTIC  COMA.  167 

sequences  of  dilatation  of  the  stomach,  it  has  appeared  to  me  in 
several  cases  that  osteomalacia,  in  the  adult,  may  receive  a 
similar  interpretation. 

En  resume,  it  seems  to  follow,  from  the  existence  of  so 
man}'  organic  and  functional  troubles  in  people  the  subjects  of 
dilatation  of  the  stomach,  that  there  is  created  in  the  organism 
a  special  aptitude  for  the  tissues  to  become  inflamed,  and  for 
perversions  of  nutrition  to  arise,  from  which  result  fragility  of 
some  part  of  the  tissues  and  changes  in  the  form  of  others. 

What  has  occasioned  surprise  among  many  physicians,  when  I 
have  pretended  to  establish  a  relationship  of  cause  and  effect 
between  dilatation  of  the  stomach  and  the  other  symptoms 
which  are  associated  with  it,  is  the  variety  of  these  symptoms, 
which  a  simple  change  of  form  of  that  viscus  is  incapable  of 
explaining  to  them.  Numerous,  however,  are  the  local  diseases 
which  take  their  hold  upon  the  organism. 

For  a  long  time  past,  since  Beau  and  before  him,  we  have  known 
how  dyspepsias  cause  an  impression  upon  the  nervous  system,  the 
feelings,  movements,  nerves  of  the  vascular  system,  and  ideation  ; 
we  have  admitted  that  certain  nervous  symptoms,  contracture 
of  the  extremities,  may  be  induced  by  gastro-intestinal  trouble. 
Whatever  the  disease  of  the  stomach  may  be,  certain  functional 
disturbances  are  sufficient  to  cause  the  development  of  dyspeptic 
coma,  which,  symptomatically,  is  identical  with  diabetic  coma. 

This  coma  has  been  seen  in  cancer,  chronic  ulcerative  gas- 
tritis, and  I  have  seen  it  in  dilatation  of  the  stomach.  Jacksch 
and  Senator  have  properly  described  it.  There  is,  at  first,  agi- 
tated movement,  jactitation ;  then  comes  a  gradual  somnoles- 
cence,  rapidly  changing  into  coma.  We  notice  a  singular 
form  of  dyspnoea, — twenty  or  thirty  respirations  only  per  min- 
ute, but  constituted  by  a  deep  and  laborious  inspiration,  with 
great  movement  of  the  larynx  and  a  moaning,  panting  expira- 
tion. The  temperature  is  normal;  the  pulse  small,  frequent, and 
compressible.  The  odor  of  the  breath  recalls  that  of  chloroform  ; 
probably  it  is  due  to  the  same  substance  as  that  which  is  exhalrd 
in  the  breath  of  diabetics,  since  we  find  it  in  urine  with  the 
same  chemical  reaction.  It  has,  besides,  been  also  noticed  in 
leucocytluemia  and  pernicious  anu-mia. 


168  LECTURES  ON   AUTO-INTOXICATION. 

Is  it  astonishing,  therefore,  that  severe  nervous  symptoms 
should  be  caused  by  a  simple  dilatation  of  the  stomach  ? 

What  occurs  in  the  chronic  gastroenteritis  of  infants  due  to 
a  defective  or  premature  alimentation  ?  At  first  there  appears 
green,  acid  diarrhoea,  which  excoriates  the  buttocks;  then  arise 
subsequent  phenomena, — fever,  cutaneous  eruptions  (erythema- 
tous,  eczematous,  and  pustular),  and,  lastly,  the  peculiar  nodosi- 
ties of  rachitis.  These  are,  really,  alterations  of  the  bony  tissue, 
induced  by  a  primary  disease  of  the  stomach. 

It  has  been  accepted,  but  not  without  difficulty,  that,  the 
kidney  being  diseased,  there  may  result  from  it  general  disturb- 
ances,— dropsies,  nervous  accidents,  headache,  pruritus,  deaf- 
ness, amaurosis,  dyspnoea  from  functional  trouble  of  the  heart, 
but,  also,  modifications  in  the  structure  of  the  heart ;  hypertrophy 
of  the  left  ventricle  with,  as  a  stethoscophic  sign,  reduplication 
of  the  first  sound.  It  has  been  thoroughly  acknowledged,  be- 
cause each  fact  was  presented  in  an  isolated  and  successive  man- 
ner, that  all  these  conditions,  so  varied,  arise  from  disease  of 
the  kidney.  I  believe  that,  in  the  same  manner  with  regard  to 
dilatation  of  the  stomach,  we  will  come  to  recognize  the  fact  that 
the  accidents  so  varied  which  accompany  it  are  really  subordi- 
nated to  it. 

If  I  am  of  this  opinion,  it  is  because  I  represent  to  myself 
the  kidney  as  an  organ  with  a  functional  dignity  inferior  to 
that  of  the  digestive  canal ;  it  eliminates  matter  without  alter- 
ing it;  and  j'et,  what  disturbances  its  diseases  cause  in  the 
organism ! 

What  can  it  be,  therefore,  which  passes  when  the  stomach  is 
at  fault,  the  functional  derangement  of  which  disturbs  the  whole 
intestine  ?  How  is  it  possible  for  its  derangement  not  to  affect 
the  whole  organism  ?  Think  of  the  physiological  importance  of 
the  digestive  tube.  It  introduces  into  the  organism  all  the  solid 
and  liquid  material, — all  except  oxygen, — and,  before  introducing 
the  material,  it  must  elaborate  it.  It  has,  therefore,  not  only  to 
play  the  part  of  an  emunctory,  but  its  functional  derangement 
must  vitiate  part  of  the  emunctory  apparatus  and  the  cells  of 
all  the  organism. 

Some  people  are  willing  to  admit  the  reality  of  the  symp- 


AFFECTIONS   OF   JOINTS.  169 

toraatic  grouping  which  I  have  indicated,  but  they  do  not  con- 
sider that  all  the  associated  symptoms  may  be  subordinated  to 
the  stomach;  there  would  be  links  established  between  them  and 
it,  but  no  subordination.  As  in  certain  cases  of  dilatation  we 
find  re-united  several  symptoms  which  recall  arthritism,  nodosi- 
ties of  joints,  migraine,  neuralgias,  sibilant  bronchitis,  eczema, 
:md  as  arthritism  determines  dyspepsia  accompanied  by  a  cer- 
tain degree  of  laxity  of  the  stomach,  we  are  forced  to  rely  upon 
this  coincidence,  so  as  to  say  that  dilatation  of  the  stomach  is 
only  one  of  the  consequences  of  arthritism,  like  the  other 
symptoms  of  which  I  have  just  spoken. 

But  this  assemblage  of  symptoms  of  an  arthritic  nature  is 
only  the  small  coin,  as  it  were,  of  arthritisra !  They  are  dis- 
orders which  may  arise  outside  of  the  arthritism  ;  they  are  not 
the  grand,  fundamental  signs  of  the  diathesis;  it  is,  so  to  speak, 
arthritis  minor.  We  have  in  this  enumeration  met  with  neither 
diabetes  nor  gout.  These  are  two  diseases  which  are  not  met 
with  outside  of  arthritism ;  on  the  contrary,  dilatation  of  the 
stomach  is  rare  amongst  diabetics  and  the  gouty.  The}7  may, 
nevertheless,  arise  in  such  by  way  of  d}-spepsia,  should  they  be 
dyspeptic,  and  yet  great  eaters ;  for  they  accumulate  one  meal 
upon  the  preceding  one  not  digested ;  they  thus  take  meals 
irregularl}r,  and  in  too  great  quantity.  I  do  not  say  that  arthri- 
tism is  not  concerned  as  a  predisponent  in  the  pathogenesis  of 
certain  dilatations  of  the  stomach.  But  there  is  another  influ- 
ence, the  direct  heredity  of  this  organic  disposition.  We  very 
often  see  a  mother  and  her  four  children  the  subjects  of  dilata- 
tion. Is  it  because  they  live  in  common  and  in  the  same  manner, 
and  undergo  the  same  hygienic  trials  ?  No  ;  it  is  that  there  are 
families  in  whom  the  stomachs  have  a  congenital  tendency  to 
undergo  dilatation. 

In  a  ward  in  the  hospital,  out  of  ten  patients  taken  at  ran- 
dom, you  will  find  three  with  dilatation.  This  frequency  of 
dilatation  in  the  class  of  people  attending  hospital,  and  which  is 
less  predisposed  to  arthritism,  agrees  little  with  the  opinion 
which  would  see  in  dilatation  of  the  stomach  an  affection  of  an 
arthritic  nature.  It  is  true  that,  in  our  time,  men  of  the  work- 
ing class  have  borrowed  from  the  governing  classes  a  certain 


170  LECTURES   ON    AUTO-INTOXICATION. 

number  of  their  faults  and  vices  of  Irygiene.  But  I  have  little 
hope  in  convincing  the  generation  to  which  I  belong.  When 
one  has  taken  up  a  certain  line  of  study  he  does  not  care  to 
leave  it  to  undertake  another.  I  address  myself,  therefore, 
chiefly  to  those  who  are  now  receiving  their  education,  and  I 
ask  them  to  affirm  my  statements.  It  is  not  by  immediate  dis- 
cussion that  one  can  settle  such  questions,  but  only  by  facts. 
And  yet,  amongst  those  who  attack  my  manner  of  viewing  them, 
how  many  of  them  are  there  who  have  ever  thought  of  seeking  for 
dilatation  of  the  stomach  amongst  all  patients  ?  Amongst  those 
who  may  wish  to  do  so,  how  many  of  them  know  how  to  do  it? 
And,  amongst  those  who  can  seek  for  the  existence  of  a  dilata- 
tion, how  few  are  preoccupied  with  the  greatness  of  the 
question?  If  we  now  examine  under  what  appearances  dilata- 
tion of  the  stomach  is  presented  to  us,  we  are  led  to  recognize 
several  clinical  types  of  it. 

There  exists  a  latent  form ;  it  is  the  most  frequent,  since  it 
constitutes  two-thirds  of  the  cases.  No  abnormal  sensation  is 
complained  of  by  the  patient ;  no  functional  trouble  is  revealed 
on  his  being  interrogated.  Only  a  careful  examination  of  all 
the  organs  can  alone  enable  us  to  recognize  the  physical  signs 
of  dilatation  of  the  stomach.  In  the  dyspeptic  form,  the 
patient  complains  of  pains,  of  slowness  of  digestion,  and  often 
of  constipation.  The  hepatic  form  is  constituted  by  congestion 
of  the  liver,  which  shows  itself  by  increased  size  in  the  volume  of 
this  organ  and  sensation  of  weight  in  the  right  hypochondrium. 
It  is  sometimes  accompanied  by  jaundice,  and  frequently  appears 
in  young  subjects,  which  is,  perhaps,  the  explanation  of  the 
chronic  jaundice  of  infancy. 

There  exists  a  form  which  simulates  biliary  lithiasis ;  pseudo- 
gastralgic  pains,  which  are  often  really  gastralgic,  show  them- 
selves slowly,  when  intestinal  digestion  commences.  Owing  to 
the  hydrochloric  acid  being  deficient,  acetic  acid  is  produced  in 
excess,  and  irritates  the  mucosa  of  the  intestinal  tract.  We 
should  include  movable  kidney  rather  in  the  renal  form,  although 
it  depends  upon  repeated  congestions  of  the  liver. 

To  the  neurosal  type  belong  vertigoes,  depression  in  the 
mornings,  migraine,  vascular  spasms  of  the  fingers,  spinal  irrita- 


ORGANS   AFFECTED.  171 

tion,  cerebro-cardiac  neurosis,  hj'pochondriasis,  contractures  of 
the  extremities. 

The  cardiac  form  includes  palpitations,  breathlessness,  beat- 
ing in  the  temples,  redness  of  the  face,  cardiac  anguish,  and 
false  angina  pectoris. 

The  asthmatic  form,  or  bronchitic,  is  that  in  which  coryza  is 
frequent;  in  which  glutinous  expectoration,  occluding  the 
bronchial  tubes,  provokes  laborious  cough  with  sibilant  sounds, 
which  disappear  when  the  patient  has  succeeded  in  expelling 
it. 

The  renal  form  it  is  very  important  to  recognize.  When  we 
have  established  in  a  person  an  albuminuria  which  is  not  the 
transitory  albuminuria  of  fever,  and  when  we  are  undecided  be- 
tween the  hypothesis  of  a  lesion  of  the  kidney  and  that  of  a  car- 
diac affection,  it  is  necessary  to  think  that  this  albuminuria  may 
be  of  dyspeptic  and  stomach  origin,  since  seventeen  times  in 
every  one  hundred  albuminuria  co-exists  with  dilated  stomach. 
Simultaneously,  the  same  accidents  may  exist  as  those  which 
are  under  the  dependence  of  other  albuminurias, — cardiac  hyper- 
trophy, for  example. 

Under  the  name  of  the  cutaneous  form  we  may  include 
urticaria,  acne  rosacea,  and  certain  circumscribed  eczemas,  etc. 

The  rheumatismal  form,  although  the  word  may  be  defective, 
is  characterized  by  the  predominance  of  joint  manifestations, 
which  at  once  attract  the  attention,  and  which  are  often  wrongly 
looked  upon  as  chronic  rheumatism.  To  this  form  phlebitis  is, 
perhaps,  attached.  I  have  seen  this  amongst  medical  men  who 
had  dilatation  of  the  stomach  and  who  considered  themselves 
the  subjects  of  rheumatismal  phlebitis. 

Lastly,  there  is  occasion  to  admit  an  acute  or  chronic  con- 
sumptive type.  In  the  acute  consumptive  type  the  patient  has 
always  suffered  in  his  stomach  for  ten  or  fifteen  years,  then  he 
rapidly  feels  himself  thoroughly  exhausted,  and  soon  after  he  is 
no  longer  able  to  leave  his  room, — not  even  his  bed.  The  phy- 
sician, finding  no  organic  lesion,  calls  the  case  one  of  nervous 
fever.  To  the  chronic  consumptive  type  belongs  the  case  of  so 
many  patients  who  in  the  hospitals  pass  either  for  idlers  or 
hypochondriacs. 


H2  LECTURES   ON    AUTO-INTOXICATION. 

We  could  multiply  these  types,  but  around  these  ten  ma}'  be 
grouped  all  the  other  sjnnptoms.  We  must  still  remember  the 
fact  that  dilatation  of  the  stomach  renders  the  economy  more 
vulnerable,  and  opens  the  door  to  diseases  of  debility.  Chlorosis 
amongst  young  girls  and  pulmonary  phthisis  are  often  induced 
by  dilatation  of  the  stomach.  This  latter  exists  in  two-thirds 
of  the  tubercular,  and,  if  we  have  sought  for  it  early  enough,  we 
can  convince  ourselves  that  the  physical  signs  of  dilatation 
have  sometimes  for  long  preceded  the  first  symptoms  that  may 
be  regarded  as  the  premonitions  of  tuberculosis. 

I  am,  therefore,  fully  of  the  opinion  that  dilatation  of  the 
stomach  is  the  outcome  of  a  veritable  acquired  diathesis, — a 
morbid  disposition  due  to  a  disturbance  of  the  general  nutrition. 
Do  we  not  see  it,  for  example,  induce  alterations  in  the  skeleton 
in  the  same  way  as  that  to  which  we  attribute  the  production  of 
rachitis?  If  it  is  true  that  in  rickets  it  may  be  the  formation 
of  lactic  acid  in  excess  which  hinders  the  calcification  of  the 
bones,  in  patients  attacked  with  dilatation  of  the  stomach  the 
formation  in  the  digestive  tube  and  the  absorption  of  acetic  acid 
in  excessive  quantity  perhaps  explain  the  nodosities  on  the 
fingers.  I  have  even  seen  osteomalacia  produced ;  at  least,  the 
bones  were  painful  at  the  level  of  the  ribs,  joints,  femur,  and 
pelvis.  I  have  seen  the  pain  increase  by  standing  so  as  to  render 
walking  impossible. 


LECTURE   XIX. 

DILATATION  OF  THE  STOMACH — ETIOLOGY,  PATHOOENESIS,  AND 
THERAPEUSIS. 

Causes  of  dilatation  of  the  stomach.  Hygienic  causes  :  excessive,  permanent, 
or  too  frequent  distension  of  the  stomach,  In  consequence  of  bad  alimentary 
hygiene.  Pathological  causes  :  catarrhal  or  interstitial  inflammations ;  me- 
chanical obstacles  to  the  evacuation  of  the  contents  of  the  stomach.  Physio- 
logical causes  :  insufficient  iunervation ;  congenital  or  acquired  debility  of 
the  muscular  tunic  ;  reciprocal  relations  between  typhoid  fever  and  dilatation 
of  the  stomach  ;  predisposition  of  those  suffering  from  dilatation  to  contract 

typhoid  fever. Therapeutics  based  upon  the  knowledge  of  causes.  General 

stimulants.  Alimentary  hygiene.  Regularity  and  infrequency  of  meals.  Sub- 
stantial alimentation  in  small  volume.  Choice  of  foods.  The  unsuitableness 
of  alcoholic  drinks  and  of  everything  which  keeps  up  excessive  fermentation 
in  the  stomach.  Why  insufficiently-baked  bread  is  not  easily  digested.  Re- 
cent researches  upon  the  fermentation  of  bread. Necessity  for  reducing 

the  quantity  of  drink.  How  the  dietary  which  I  propose  for  dilatation  of 
the  stomach  is  not  simply  the  dry  regimen  proposed  by  Chomel  for  dyspep- 
sia due  to  the  use  of  liquids. Milk  food  as  the  preparatory  regimen  in  the 

cure  of  dilatation.  Mixed  regimen  of  eggs  and  milk.  Regimen  of  infre- 
quent and  complete  meals.  Nutritive  enemata. Antiseptic  medica- 
tion as  an  auxiliary  to  the  dietetic  regimen  :  chloroform-water,  hydrochloric 
lemonade.  Indications  for  washing  out  the  stomach.  Treatment  of  pyrosis 

and  of  ulcerative  gastritis. Advantageous  result  of  the  above-mentioned 

regimen  :  rapid  disappearance  of  the  most  disturbing  and  most  painful 
symptoms.  Necessity  for  lengthened  continuation  of  treatment,  in  order 
to  arrive  at  a  complete  cure,  which  is  not  always  possible. 

IN  order  to  place  before  you  again,  in  a  few  words,  all  the 
knowledge  we  have  accumulated  upon  intoxication  of  intestinal 
origin,  I  recall  to  you  that, after  having  demonstrated  their  reality, 
I  have  shown  3-011  how  intoxication  may  be  the  result  of  normal 
fermentation,  if  the  kidney  is  diseased,  and  how,  with  a  healthy 
kidney,  intoxication  may  be  produced  by  abnormal  fermentation. 
Afterward,  I  have  proved  to  you  that  intoxication  of  intestinal 
origin,  from  abnormal  fermentation,  may  show  itself  in  either 
the  acute  or  chronic  state.  The  time  has  now  come  for  consid- 
ering the  therapeutics  of  this  intoxication.  I  ought  already  to 
have  dealt  with,  in  a  summary  manner,  intestinal  antisepsis, 

(173) 


174  LECTURES  ON   AUTO-INTOXICATION. 

having  been  almost  of  necessity  led  to  it,  in  order  to  interpret 
ursemia  and  to  study  its  therapeutics.  I  am  now  led  to  undertake 
this  question,  whilst  studying  the  treatment  of  intoxication 
from  chronic  dyspepsia ;  that  is  to  say,  chiefly  from  dilatation  of 
the  stomach.  But  all  the  treatment  of  chronic  intoxication 
of  digestive  origin  does  not  lie  in  intestinal  antisepsis.  It  is 
not  sufficient  to  neutralize  or  to  delay  fermentations.  Without 
neglecting  the  employment  of  charcoal,  which  fixes  the  products 
of  putrefaction,  of  iodoforrn,  and  of  naphthalin,  which  prevent 
these  from  developing,  it  is  necessary  to  address  ourselves  to 
the  physiological  actions  of  the  organism,  in  order  to  correct 
the  functional  disturbances  of  the  digestive  canal. 

We  ought,  if  we  can,  to  act  upon  the  disease  which  leads  to 
fermentation  in  the  digestive  canal  by  referring  to  its  causes,  or 
to  what  is  predominant  in  chronic  dyspepsias, — that  is,  dilatation 
of  the  stomach.  In  eight  cases  of  dyspepsia  we  find  seven 
times  an  exaggerated  distension  of  the  stomach  with  an  impos- 
sibility of  retraction.  The  causes  of  this  excessive,  permanent 
distension  are  numerous.  Some  arise  from  faulty  alimentary 
hygiene.  Excessive  distension,  too  often  repeated  and  pro- 
longed, leads  up,  more  or  less  rapidly,  to  a  forced  condition  of 
stomach.  Individuals  who  eat  too  much  or  drink  too  often 
dilate  their  stomach,  but  other  hygienic  errors  lead  to  the  same 
result.  To  eat  too  quickly,  when  we  come  to  table  with  an 
excessive  appetite,  due  to  irregularity  in  our  meals,  is  hurtful, 
for  a  very  fine  mechanical  division  of  food  is  indispensable  for 
its  digestion.  Irregularity  of  meals  has  also  for  its  conse- 
quence the  leaving  of  only  too  short  an  interval  between  certain 
meals.  A  meal  is  then  introduced  into  the  stomach,  which  still 
contains  part  of  the  preceding  one.  These  are  all  bad  hygienic 
habits,  which  mechanically  engender  dilatation  of  the  stomach. 
Other  causes  may  also  be  in  operation,  such  as  bad  teeth,  which 
prevent  good  mastication. 

We  can  remedy  all  these  causes  in  the  premonitory  period, 
but  when  the  stomach  is  thus  forced,  what  then  ?  You  will  be 
able  to  advise  a  certain  number  of  palliative  measures,  which 
will  only  bring  to  the  patient  a  minimum  of  help,  if  you  do  not 
seek  in  the  minute  analysis  of  the  elements  of  the  morbid  state 


PYLORIC   OBSTRUCTION   AND   MUSCULAR   DEBILITY.  175 

those  which  therapeutics  could  attack  with  the  greatest  chances 
of  success. 

Mechanical  distension  sometimes  follows  from  pathological 
causes, — from  an  antecedent  dyspepsia  having  determined 
habitually  too  long  location  of  food  in  the  stomach ;  from  a 
chronic  catarrh  of  the  mucous  membrane,  preventing  physio- 
logical secretion ;  cancerous  or  cicatricial  constrictions  of  the 
pylorus.  The  puckered  cicatrix  of  a  cured  ulcer  of  the  pylorus 
may  progressively  lead  up,  in  quite  a  mechanical  manner,  to 
distension  of  the  stomach,  where  digestion,  nevertheless,  is 
normal  in  operation.  "We  may  attribute  a  large  share  in  the 
pathogenesis  to  debility  of  the  muscular  wall.  General  nervous 
debility — that  state  of  irritable  debility  and  neurasthenia  which 
exists  amongst  hysterical  people  and  in  ataxies — causes  varia- 
tions in  the  energy  of  the  central  nervous  sj-stem,  whence  there 
results  distension ;  but  this  is  rarely  permanent.  We  notice,  too, 
an  intermittent  distension  in  exophthalmic  goitre,  in  convales- 
cence from  serious  affections,  after  grief,  prolonged  indisposition, 
sad  mental  preoccupation.  All  these  distensions  have  not  }-et 
become  dilatation,  but  may  end  in  it.  It  is  also  necessary  to 
take  cognizance  of  the  radical  debility  of  such  and  such  a  tissue 
in  certain  people,  in  consequence  of  which,  in  the  pathogenesis 
of  dilatation  of  the  stomach,  there  is  occasion  given  for  the 
influence  of  heredit}'.  It  is  certain  that  in  the  same  famil}'-  dila- 
tation of  the  stomach  exists  amongst  several  individuals,  without 
our  being  able  to  call  to  our  aid,  in  order  to  explain  it,  a  group 
of  hygienic  defects.  It  may  be  said  of  the  stomach,  as  of  the 
scrotum,  which  is  habitually  retracted  in  certain  people,  that  there 
is  a  weak  condition  in  some,  owing  to  a  natural  muscular  debility. 

Lastly,  debility  of  the  muscular  wall  of  the  stomach  may  be 
the  result  of  a  morbid  degeneration.  The  study  of  degenera- 
tions of  the  muscular  wall  has  been  made  in  the  intestine  by 
Blaschko,  Sasaky,  Nothnagel,  and  Schleimpflug.  They  have  seen 
atrophy  to  be  the  result  of  fatty  degeneration  of  the  muscular 
tunic  itself,  consecutive  to  inflammatory  affections  of  the  mucous 
membrane,  to  intemperance,  or  to  habitual  alcoholic  intoxica- 
tion, to  lesions  of  the  intestinal  and  central  nervous  system, 
and,  lastly,  to  infectious  diseases. 


176  LECTURES   ON   AUTO-INTOXICATION. 

These  causes  are  probably  attributable  to  debility  of  the 
gastric  muscular  wall.  After  typhoid  fever  it  is  developed ; 
oftener  it  arises  at  the  beginning  and  even  before  the  commence- 
ment of  the  disease.  It  is  not  rare  that  t}rphoid  fever  is  devel- 
oped in  people  whose  stomach  has  already  been  dilated.  I  have 
seen,  in  the  course  of  these  two  last  years,  twelve  cases  of 
typhoid  fever  in  my  practice  at  the  hospital ;  that  is  to  say, 
coming  on  in  patients  under  treatment  for  another  illness,  twelve 
times  was  there  question  of  patients  the  subject  of  dilatation  of 
the  stomach.  We  might  ask  the  question,  whether  dilatation 
had  not  prepared  the  way  for  the  introduction  of  the  infectious 
agent  ?  I  content  myself,  for  the  moment,  by  an  empirical 
statement  of  the  fact.  The  largest  number  of  patients  whom  we 
treat  in  the  hospitals  for  typhoid  fever  carry  nodosities  on  the 
second  articulations,  which  prove  that  dilatation  was  the 
primary. 

If  these,  therefore,  are  the  varied  causes  which  may.,  take 
part  in  dilatation  of  the  stomach,  what  resources  may  their 
knowledge  furnish  us  with  for  their  therapeutics  ?  Nothing  of 
consequence,  save  two  things.  If  there  exist  habitually  a  con- 
dition of  primary  dyspepsia,  aggravated  recently,  it  will  be 
advisable  to  combat  this  dyspeptic  state,  in  order  to  allow 
the  stomach  to  become  retracted.  If  the  nervous  system  should 
increase  the  retractility  of  what  remains  of  healthy  muscular 
fibres,  general  stimulants  can  indirectly  give  advantageous 
results ;  they  will  not  cure,  but  they  will  aid  in  the  cure.  We 
may  stimulate  directly  the  nerve  terminations  in  the  gastric  wall 
by  simple  bitters  and  astringent  bitters.  We  may  give  attention 
to  the  general  nervous  system  in  its  cutaneous  and  peripheral 
expansions ;  we  may  prescribe  dry  or  aromatic  friction,  change 
of  air,  high  altitudes,  sea-air.  It  is  necessary  to  remove  all 
care,  preoccupation,  and  to  procure  distraction  by  traveling 
and  pleasurable  occupation.  Distraction  is  particularly  neces- 
sary during  meals,  which  it  is  well  to  take  in  pleasant  company. 
These  are  small  measures,  but  their  utility  is  beyond  question. 
We  might  derive  benefit  from  the  cold  or  hot  douche,  or  the 
shower  bath,  with  ordinary  water,  or  that  containing  sulphur  or 
saline  material.  We  need  not  ask  how  a  cutaneous  douche 


PRINCIPLES   OF   ALIMENTARY   HYGIENE.  177 

revives  the  stomach  ;  it  is  simply  a  question  of  improving  function. 
With  a  bad  tool  a  workman  may  do  pretty  good  work.  Sulphur- 
ous and  saline  baths,  sea-baths,  cold  baths,  and  baths  of  Plom- 
bieres  may  be  useful.  I  can  scarcely  believe  in  the  favorable 
influence  of  electricity,  in  spite  of  the  results  of  which  some 
have  made  a  great  noise.  They  publish  at  first  the  successful 
cases,  and  they  forget  to  mention  the  others.  Inhalations  of 
oxygen  sometimes  answer  well ;  these  improve  the  appetite  and 
stimulate  digestion. 

Lastly  and  chiefly,  we  must  pay  attention  to  alimentary 
hygiene.  This  includes  the  whole  of  the  means  which  cause 
digestion  to  be  rapid,  and  which  thus  prevent  a  protracted  stay 
of  food  in  the  stomach.  We  may  put  it  in  the  following  axiom  : 
it  is  necessary  that  the  stomach  should  be  distended  the  least  pos- 
sible, least  often,  and  for  the  shortest  time  possible.  We  must  first 
masticate  well;  consequently,  certain  buccal  preparations  are 
sometimes  necessary.  We  must  eat  slowly,  and  without  mental 
worry.  It  is  necessary  to  abstain  altogether  from  work  immedi- 
ately after  meals.  Fatiguing  work  is  bad,  even  if  it  is  physical 
work ;  what  is  useful  is  no  longer  repose,  but  muscular  activity 
in  the  open  air,  without  it  being  pushed  to  the  extent  of  fatigue. 

There  must  be  neither  eating  nor  drinking  between  meals. 
The  meals  must  be  widely  separated  from  each  other.  To  eat 
once  a  day  is  impossible.  If  we  only  make  two  meals,  should 
these  be  separated  b}r  twelve  hours?  No ;  the  needs  of  the 
organism  are  much  less  during  the  period  given  up  to  repose. 
We  must  allow  nine  hours  between  the  two  meals  as  the  interval 
by  day,  and  fifteen  hours  as  the  interval  by  night.  This  infre- 
quency  of  meals  is  sometimes  sufficient  to  cause  heartburn  to 
disappear  and  the  sensations  of  heat,  and  to  arrest  the  emacia- 
tion of  patients  who  should  moderate  their  appetite  in  order  to 
prevent  their  pains.  As  a  rule,  we  must  allow  to  patients  three 
meals  per  diem,  with  an  interval  of  eight  hours  between  the  two 
principal  ones  and  four  hours  between  the  first  and  second. 
We  must  make  exception  for  growing  children.  The  hours 
should  be,  for  example,  7.30  and  11.30  in  the  forenoon,  and  7.30 
in  the  evening.  In  the  cases  where  this  interval  is  not  sufficient 
for  the  digestion  of  the  preceding  meal  to  be  completed,  it  will 


178  LECTURES   ON   AUTO-INTOXICATION. 

be  necessary  to  proceed  with  the  artificial  evacuation  of  the 
stomach. 

The  meals  ought  not  to  be  copious,  but  substantial.  It  is 
advisable  to  suppress  all  that  is  unnecessary  and  made  with 

water, consequently,  liquid  foods.  Yet  it  is  necessary  to 

give  sufficient,  and  even  a  little  more,  because  the  organism 
may  be  obliged  to  eliminate  an  excess  of  solid  material  l>y  the 
urine,  which  can  only  be  done  by  the  help  of  a  determined 
quantity  of  water.  We  must  never  expose  ourselves  to  the 
attempt  to  reach  the  limit  on  this  side  of  which  urinary  depura- 
tion might  be  prevented.  We  would  not  allow  liquids  at  other 
than  meal-times ;  375  grammes  of  drink  at  each  meal,  or  three- 
fourths  of  a  litre  in  twenty-four  hours,  ought,  in  a  general  way, 
to  be  sufficient. 

As  digestion  requires  that  the  foods  should  be  not  only 
softened,  but  penetrated  by  the  gastric  juice,  they  must  not  be 
fatty.  The  stomach  is  not  called  upon  to  digest  fat,  but  the 
latter  might  prevent  the  stomach  from  digesting  what  it  ought, 
by  preventing  the  hydrochloric  acid  of  the  gastric  juice  from 
softening,  penetrating,  and  hydrating  meat  and  other  alimentary 
substances.  It  is  better  still  to  have  the  fat  emulsionized,  as  in 
milk.  The  food  ought  to  be  as  much  divided  as  possible ;  we 
must,  therefore,  prescribe  food  easy  of  mastication, — not  hard 
food,  but  cold  or  very  well  cooked  meat  and  boiled  fish.  It  is 
necessaiyto  avoid,  as  much  as  possible,  everj'thing  that  may  have 
a  tendency  to  undergo  fermentation, — alcohol,  which  furnishes 
acetic  acid,  acid  substances,  and  certain  parts  of  bread.  Wine 
is  certainly  unfavorable,  especially  red  wine,  and,  above  all,  pure 
red  wine.  But  pure  water  is  distasteful  to  certain  people,  and, 
as  they  no  longer  have  any  appetite,  they  lose  weight  if  they  are 
submitted  to  this  regimen.  In  order  to  give  the  least  amount  of 
alcohol  possible,  we  must  advise  to  be  added  to  wtiter  one-fourth 
of  white  wine,  one-third  of  beer,  or  a  teaspoonful  of  brandy. 

Bread  is  generally  badly  borne  by  dyspeptics,  but  rice, 
barley,  oatmeal,  and  unfermented  pastes  are  allowed.  As  re- 
gards bread,  we  may  allow  only  the  crust  or  grated  crumb. 
The  reason  for  this  restriction  is  this  :  Baking,  having  inter- 
rupted the  fermentation  of  the  dough,  has  not  stopped  it  alto- 


FERMENTATION    AND   THE  PROCESS   OF  BAKING.  179 

gether;  consequently,  this  fermentation  re-appears  when  moisture 
and  temperature  are  again  favorable  to  it.  In  thoroughly-baked 
bread  fermentation  is,'on  the  contrary,  entirely  stopped.  What, 
then,  is  this  fermentation  of  bread  ?  The  idea  generally  adopted 
on  the  subject  is  that  which  was  clearly  defined  by  Graham.  In 
the  presence  of  cereal! n  (diastase)  starch  is  broken  up  into 
maltose  and  dextrin.  Maltose,  under  the  influence  of  saccharo- 
myces  minor,  forms  two  sugars, — dextrose  and  Isevulose.  The 
two  sugars,  un'der  the  influence  of  the  saccharom3Tces,  ferment, 
producing  alcohol  and  carbonic  acid,  which  cause  the  bread  to 
rise. 

M.  Duclaux,  who  has  accepted  this  theory  in  principle,  denies, 
moreover,  the  existence  of  alcohol  in  this  fermentation.  The 
question  has  been  taken  up  again  by  M.  Chicandart.  The  result 
of  his  researches  is  that,  in  dough  in  process  of  fermentation,  we 
do  not  find  either  soluble  starch  or  dextrin.  The  first  part, 
therefore,  of  the  theory  of  Graham  falls.  We  do  not  find  in  it 
more  sugar  than  in  flour.  We  do  not  find  alcohol  either,  but 
in  the  fermented  dough  there  exist  acetic  and  butyric  .'ic-ids, 
supposing  we  only  employ  gluten  without  starch,  and  lactic 
acid  with  pure  gluten.  We  also  find  leucin,  ty rosin,  phenol ; 
that  is  to  say,  the  products  of  the  fermentation  of  a  nitrogenous 
substance. 

What  undergoes  fermentation  in  dough  is,  therefore,  the  glu- 
ten, which  gives  birth  to  the  products  of  acetic  fermentation  in 
the  presence  of  a  bacterium, — the  bacillus  glutinis.  But  this 
resists  the  temperature  to  which  the  centre  of  the  crumb  is 
found  to  be  carried  during  cooking ;  and  it  may,  therefore,  carry 
on  in  the  stomach  acetic  fermentation.  By  the  knowledge  of 
these  facts  is  explained  the  usefulness  of  un fermented  and  grated 
bread  in  the  feeding  of  dyspeptics. 

After  having  laid  down  the  general  rules  for  a  dietary  which 
has  for  its  aim  the  attainment  successively  of  functional  ameli- 
oration, then  the  anatomical  restoration  of  a  digestive  canal 
deteriorated  by  dilatation  of  the  stomach,  I  proceed  to  state 
precisely  the  concrete  formula  of  the  regimen. 

I  remind  you  that  meals  ought  to  be  takt'ii  :it  iv.irular  hours; 
that,  if  it  is  possible  to  obtain  consent  from  patients  for  only 


180  LECTURES   ON   AUTO-INTOXICATION. 

two  meals  in  twenty-four  hours,  these  ought  to  be  separated  by 
an  interval  of  nine  hours ;  but  that,  as  during  the  greater  part 
of  the  time  three  meals  are  necessary,  the  intervals  ought  to  be 
four  hours  between  'the  first  and  second  and  eight  hours  between 
the  second  and  third.  Thus,  the  first  meal  will  be  taken,  for 
example,  at  7.30  in  the  morning,  the  second  at  11.30,  and  the 
third  at  7.30  in  the  evening. 

The  patients  ought  to  take  nothing  between  meals,  and 
should  strongty  resist  any  impulses  of  hunger  or  thirst,  when 
even  this  resistance  would  cause  them  suffering,  and  in  spite  of 
the  momentary  relief  which  satisfaction  of  these  desires  would 
appear  to  give  them.  We  will  frequently  secure  from  patients 
this  difficult  resignation  when  we  have  clearly  made  them  under- 
stand the  necessity,  and  when  we  have  dazzled  them  with  the 
hope  of  a  definite  and  absolute  cure.  Meals  should  be  taken 
slowly,  and  mastication  should  be  slow  enough  to  reduce  the 
aliments  into  pulp. 

It  is  necessary  to  insist  upon  the  prohibition  of  liquid  ali- 
ments which  dilute  the  gastric  juice,  and  of  fats  which  remove 
from  the  action  of  this  juice  the  solid  alimentary  substances,  and 
to  insist,  also,  upon  the  advisability  of  eating  only  a  little  bread. 

The  early  breakfast  should  not  be  abundant :  an  egg,  cooked 
fruits,  or  marmalade, — neither  bread  nor  drinks.  At  the  second 
meal  there  should  be  cold  meats  (well  cooked),  hot  meats  (but 
broiled  in  preference  to  underdone  roasts),  meat-soups,  boiled 
fish,  eggs  lightly  cooked,  eggs  prepared  in  milk,  milk  in  some 
way  solidified,  paste  (e.g.,  vermicelli)  ;  rice  prepared  in  milk,  or 
in  soup,  or  with  the  juice  of  meat;  vegetable-soups  (considered, 
wrongly,  as  increasing  flatulent  dyspepsia),  cheese,  comp6tes  of 
fruit.  Of  fresh  fruits  these  only  will  be  allowed  :  strawberries, 
peaches,  and  grapes.  I  do  not  know  why  the}'  are  better  digested 
than  other  fruits  by  dyspeptics,  but  I  indicate  the  fact  to  you  as 
the  result  of  experience.  Other  fruits  should  only  be  allowed 
cooked. 

The  important  advice  as  regards  drinks  is  resumed  in  the 
instruction  not  to  drink  at  the  first  meal  nor  between  meals,  and 
not  to  drink  at  any  of  the  two  principal  meals  more  than  a  glass 
and  a  half,  each  glass  containing  250  grammes  (£  litre).  In  the 


EATING   AND  DRINKING:    INDICATIONS   TO   BE   FULFILLED.        181 

summer-time,  for  patients  who  perspire  profusety,  we  would 
moderate,  somewhat,  the  rule,  in  order  to  make  some  compensa- 
tion for  the  loss  of  liquid.  Drink  should  be,  by  preference,  pure 
water;  alcohol  ought  to  be  avoided,  because  it  gives  rise  to 
acetic  acid.  But,  our  habits  being  repugnant  to  the  use  of  pure 
water,  we  would  advise  the  addition  to  the  water  of  one-third 
beer  or  one-fourth  of  white  wine ;  we  would  reject  red  wine, 
which  contains  too  much  alcohol  and  tannin,  also  the  infusion 
of  tea. 

It  has  been  wrongly  stated  that  the  regimen,  thus  formulated, 
was  the  dry  regimen  already  laid  down  by  Chomel.  But  the 
whole  regimen,  according  to  Chomel,  was  limited  to  the  sup- 
pression of  liquids.  Mine  proposes  to  satisfy  three  indications; 
to  obtain  these  gastric  distension  should  be  slight,  infrequent, 
and  of  short  duration. 

In  order  to  bring  about  the  first,  I  am  willing  to  give  sufficient 
alimentation  in  the  smallest  volume  possible.  I  moderate  the 
employment  of  water,  both  because  it  occupies  space  and  dilutes 
the  gastric  juice.  Chomel  has  seen  dyspepsia  from  liquids 
which  is  real  and  which  may  coincide  with  certain  cases  of  dila- 
tation of  the  stomach,  but  not  with  all;  the  dyspepsia  of  liquids 
is  not  dilatation  of  the  stomach. 

The  second  indication  requires  that  the  meals  should  be 
infrequent. 

The  third  is  fulfilled  by  the  emplo3rment  of  solid  foods,  easy 
to  digest  and  very  finely  divided,  in  order  that  the  surface  of 
digestion  may  be  increased.  I  exclude  aliments  easily  trans- 
formable into  acetic  acid  ;  that  is  why  I  reduce  alcohol  to  a 
minimum  ;  and  I  suppress  bread,  which  I  only  allow  transformed 
into  crust  or  toasted. 

This  regimen,  such  as  I  have  just  formulated,  presupposes 
that  there  is  still  great  digestive  power.  In  a  certain  mnulu'r 
of  cases,  neither  meat  nor  farinaceous  vegetables  are  digested. 
What  is  to  be  chosen,  then,  the  dry  regimen?  No;  but  milk 
diet,  on  condition  of  instituting  it  according  to  the  precepts 
laid  down  by  Cruveilhier  for  the  treatment  of  ulcer  of  the 
stomach,  in  frequent  doses  and  in  small  quantities,  in  order  that 
its  digestion  may  be  rapid  and  complete.  Milk  diet  is  a  prepar- 


182  LECTURES  ON   AUTO-INTOXICATION. 

atory  regimen.  We  should  begin  with  the  quantity  strictly 
necessary  to  prevent  deterioration  of  the  organism, — 1  table- 
spoonful  every  two  hours,  if  it  is  advisable;  then  1  litre  daily 
in  ten  equal  doses;  that  is  to  say,  100  grammes  every  two 
hours, — from  6  or  7  o'clock  in  the  morning  to  10  or  11  o'clock 
at  night, — nine  doses  in  the  day ;  one  during  the  night.  By 
increasing  progressively  each  dose,  we  reach  2  litres  in  the 
twenty -four  hours,  which  are  sufficient  for  the  sustenance  of  any 
man.  Lastly,  2^  litres,  in  ten  doses  of  250  grammes,  should  not 
be  exceeded.  And  then  we  should  proceed,  by  insensible  transi- 
tion, to  mixed  diet.  We  add,  first,  a  }relk  of  an  egg  to  one  of  the 
cups  of  milk,  then  to  several,  which  brings  us  up  to  ten  yelks 
of  eggs.  At  this  period  we  would  replace,  at  10  o'clock  in  the 
morning,  the  cup  of  milk  by  rice-soup,  barley,  oats,  oatmeal,  or 
paste,  but  suppressing  the  cup  at  midday,  in  order  to  allow  the 
stomach  four  hours  to  digest  the  soup.  In  the  evening  the 
same  substitution  should  be  made  at  6  o'clock.  After  a  week 
of  these  two  light  meals,  suppressing  four  cupfuls  of  milk,  we 
can  then  add  a  whole  egg  to  the  soup ;  then  fish  or  cold  fowl  at 
the  morning  meal,  and  at  that  of  the  evening  clear  soup  of 
potatoes.  From  this  time  onward  we  may  boldly  approach  the 
diet  of  two  complete  meals  in  the  twenty-four  hours ;  then  we 
may  alternately  add,  if  necessary,  the  small,  supplementary  meal 
of  the  morning. 

Sometimes  from  the  first  it  may  be  necessary  to  maintain  the 
patient  a  little  more,  if  his  weakness  is  excessive,  or  to  beguile 
his  thirst.  We  may  have  recourse  to  alimentary  drinks  or  to 
nutritive  enemata.  We  may  employ  aqueous  solutions  of  pep- 
tones, properly  prepared,  which  we  now  find  procurable  in 
France,  and  which  have  nothing  in  common  with  the  products 
falsely  sold  for  a  long  time  under  this  designation.  Or  shall  we 
be  obliged  to  have  recourse  to  alimentary  powders  (to  meat 
powder),  which  have  been  of  signal  service  in  certain  diseases 
in  which  it  was  necessary  to  maintain  nutrition  ?  I  do  not  think 
so.  They  have,  doubtless,  the  advantage  of  being  very  finely 
divided,  but  they  remain  difficult  of  digestion,  because  they  nau- 
seate. We  cannot  dispense  with  the  part  which  the  nervous 
system  plays  in  the  cure  of  the  diseases  of  the  stomach ;  the 


HOW    TO    PREVENT   FERMENTATION   IN    THE   STOMACH.  183 

patient  who  swallows  with  dislike  does  not  digest.     It  would  be 
better,  in  case  of  need,  to  allow  any  fine  pulp  of  cooked  meat. 

In  order  to  prevent  the  excessive  fermentation  which  dilata- 
tion of  the  stomach  favors,  we  should  have  recourse  to  the  anti- 
septic method.  Many  antiseptics  are  at  our  disposal.  Creasote 
(which  has  been  employed  for  more  than  thirt}r  }'cars,  in  acid 
dyspepsias  particularly),  iodoform,  and  naphthalin  fail,  very 
often,  because  they  spoil  the  appetite;  salicylic  acid,  in  a  suf- 
ficient dose  to  be  truly  antiseptic,  induces  nervous  derange- 
ments ;  salicylate  of  bismuth,  less  soluble,  is  also  less  active. 
Chloroform-water  is  better;  oxygenized  water  is  good ;  but  what 
is  better  still  is  hydrochloric  acid,  which  prevents  anomalous 
fermentations  and  aids  physiological  digestion.  No  fermenta- 
tion is  possible  in  a  liquid  which  contains  for  every  1000  parts 
1.10  grammes  of  anhydrous  hydrochloric  acid,  equivalent  to  3.30 
grammes  of  the  fuming  hydrochloric  acid  of  commerce.  The 
liquor  which  I  employ  is  a  solution  with  this  formula : — 

Fuming  hydrochloric  acid,  pure,         .        .          4  grammes. 
Water, 1000  grammes. 

It  is,  generally  speaking,  neither  disagreeable  nor  irritating. 
It  is  a  little  painful  to  some  patients, — cancerous  particularly,  or 
those  who  have  ulcerations  lying  upon  the  great  curvature.  We 
may  give  it  at  one  meal,  only  in  the  dose  of  a  few  mouthfuls  dur- 
ing the  course  of  the  meal,  or  a  glassful  at  the  end  of  it.  We 
may  give  as  much  as  750  grammes  of  the  solution  apart  from 
the  meals.  When  digestion  is  not  terminated  three  or  four 
hours  after  the  meal,  we  must  come  to  the  aid  of  the  stomach 
by  replacing  its  exhausted  secretions.  As  a  help,  I  ought  to 
speak  of  the  practice  of  washing-out,  so  much  in  vogue  for  the 
last  few  years.  It  has  given  satisfaction  on  the  old  erroneous 
idea  that  fluids  which  have  accumulated  in  the  stomach  ought  to 
be  removed.  The  real  service  which  it  renders  is,  to  free  the 
stomach  of  the  remains  of  previous  digestions  not  attacked  by 
the  gastric  juice  and  undergoing  putrefaction. 

Washing  out  the  stomach  does  not  cure  dilatation,  it  can 
only  relieve  some  of  its  consequences  ;  and  as  for  its  advantages, 
these  are  accompanied  by  certain  inconveniences, — e.0.,the  dim- 


184  LECTURES   ON   AUTO-INTOXICATION. 

inution  of  the  appetite  and  of  digestion,  and,  in  consequence, 
increase  of  emaciation.  Nevertheless,  it  is  a  necessary  method 
under  certain  circumstances.  We  ought  to  lay  it  down  as  a 
principle  that  we  should  never  introduce  an  additional  meal  into 
the  stomach  when  the  previous  one  has  not  been  digested.  Five 
hours  after  ingestion  the  presence  of  food  in  the  stomach  is 
pathological,  and  from  the  sixth  hour  onward  there  will  occur 
in  this  alimentary  mass  anomalous  fermentation.  Beyond  the 
seventh  hour  the  alimentary  residue  will  undergo  exclusively 
acid  or  putrid  fermentation.  When,  therefore,  rational  signs  or 
exploratory  catheterization  shall  have  established  stagnation  of 
the  alimentary  residue  in  the  stomach,  there  will  be  formal 
reasons  for  evacuating  it.  Then  we  can  leave  the  stomach  to 
rest  for  two  hours,  to  recover  itself,  so  to  speak.  Patients 
undergoing  lavage  ought  to  have  only  two  meals  per  diem.  At 
the  same  time  you  should  make  antisepsis;  but,  in  order  to 
attain  this  end,  no  liquid  is  necessary.  We  cannot  introduce 
hydrochloric  acid  into  an  empty  stomach,  especially  as,  in  these 
cases  of  putrid  stagnation,  there  exists  already  upon  the  greater 
curvature  punctated  haemorrhages  and  ulceration  of  the  mucous 
membrane.  But  there  is  no  inconvenience  whatever  in  intro- 
ducing iodoform  (in  pill),  creasote,  or  nitrate  of  silver,  which 
may  be  useful  in  overcoming  pyrosis.  This  extremely  painful 
symptom  yields  too,  generally  speaking,  after  a  few  days  of 
regimen,  without  the  employment  of  medicines. 

When  pain  is  such  that,  in  spite  of  the  stoicism  which  you 
would  like  to  inspire  in  your  patient,  it  is  necessary  to  intervene 
to  give  him  immediate  relief,  we  can  neutralize  the  corrosive 
acids  which  cause  such  great  pain  by  means  of  sodium  bicarbo- 
nate, prepared  chalk,  calcined  magnesia,  charcoal,  to  all  of 
which  may  be  added  a  small  quantity  of  opium  or  combined 
with  chloroform-water,  which  relieves  pain  and  checks  fermenta- 
tion ;  finally,  cocaine  may  render  some  service  in  diminishing 
the  sensibility  of  the  mucous  membrane.  When  ulceration  of 
the  stomach  supervenes,  the  therapeutic  indications  are  those 
laid  down  by  Cruveilhier.  The  patient  is  then  in  a  grave  con- 
dition, having  reached  a  very  advanced  stage  of  the  illness. 

In  making  an  abstract  of  the  cases  in  which  patients  come 


GASTRIC   DILATATION   AND   ITS  PROSPECTS   OP   CURE.  185 

to  you  only  in  the  last  stages  of  their  illness,  you  will  derive 
great  benefit  always  from  the  dietetic  and  therapeutic  rules 
which  I  have  just  laid  down.  You  will  sometimes  see  patients 
who  have  suffered  for  ten  years  lose  their  suffering  at  the  end 
of  two  days,  and  declare  themselves  cured  at  the  end  of  three 
weeks.  Remember  that  this  is  not  even  an  apparent  cure,  and 
that  all  the  symptoms  will  re-appear  on  the  day  following  that 
on  which  the  regimen  has  been  abandoned. 

At  the  end  of  what  time,  then,  can  we  hope  for  a  cure?  In 
the  case  of  certain  stomachs,  dilated  from  the  period  of  infancy, 
cure  will  never  be  realized  ;  but,  thanks  to  the  permanence  of 
the  treatment,  we  can  overcome  the  anatomical  imperfection  of 
the  organ.  The  largest  number  of  patients  can,  nevertheless, 
be  cured,  but  not  in  less  than  two  years ;  and  these  cures  are 
easily  broken.  Long  before  the  cure  of  the  gastric  symptoms 
you  will,  fortunately,  have  the  satisfaction  of  seeing  disappear 
the  superadded  diseases,  unless  phthisis  is  part  of  the  morbid 
process  and  the  mushroom  bacillus  has  developed  upon  the 
waste  which  the  organism  has  supplied  to  it.  There  are  nervous 
symptoms  which  may  yield  at  the  end  of  a  few  hours,  even  cer- 
tain sibilant  rales  of  bronchitis,  which  arise  from  intoxication, 
and  are  due  to  gastric  fermentation  ;  certain  anginal  cardiac 
symptoms  (dyspnoeal),  and  the  cutaneous,  and  especially  renal, 
manifestations.  Albuminuria  rapidly  improves  and  totally  dis- 
appears, at  the  same  time  that  it  is  accompanied  by  cardiac  re- 
duplication. The  alterations  in  the  joints,  caused  and  main- 
tained by  the  excess  of  acetic  fermentations,  may  even  retrocede. 

The  possibility  of  obtaining  similar  results  is  a  reason,  in 
my  opinion,  for  insisting  upon  the  indications  to  be  fulfilled  and 
the  rules  to  be  followed  in  the  treatment  of  chronic  intoxication 
of  a  digestive  origin,  the  type  of  which  is  dilatation  of  the 
stomach.* 

*  Since  these  lectures  were  delivered,  M.  P.  le  Gendre  has  studied  more  par- 
ticularly certain  points  in  the  history  of  dilatation  of  the  stomach,  and  he  has  pub- 
lished the  result  of  his  researches  in  an  inaugural  thesis,  "Dilatation  of  the  Ktonmch 
and  Typhoid  Fever.  Scmeiological  Value  of  the  Nodosities  of  Bouchard." 

M.  le  Gendre  has  commenced  by  fixing  the  mean  capacity  of  the  stomach  of  the 
adult,  estimated  in  cubic  centimetres  of  water,  basing  his  remarks  upon  an  examina- 
tion of  sixty  stomachs  of  cadavera  taken  hap-hazard  ;  he  believed  that  he  might  con- 
clude that  this  average  was  less  than  1300  cubic  centimetres.  But  in  twelve  cases,  in 


186  LECTURES  ON   AUTO-INTOXICATION. 

which  he  had  made  the  autopsy  upon  subjects  in  whom  dilatation  had  been  diagnosed 
during  life  by  "splashing"  as  the  method  adopted  for  diagnosis,  the  stomach  had  a 
cubic  capacity  of  from  1450  to  3600  cubic  centimetres. 

M.  le  Gendre  has  described  very  minutely,  from  a  morphological  and  anatomical 
point  of  view,  the  knotty  condition  of  the  phalango-phalangeal  joints  of  the  fingers, 
the  semeiological  value  of  which  I  have  made  known.  In  what  refers  to  those  who 
are  the  subjects  of  dilatation,  and  are  predisposed  to  contract  typhoid  fever,  I  am 
reminded  that,  in  nineteen  cases  of  this  disease  which  have  come  under  my  care 
within  the  last  two  and  a  half  years,  the  contagion  had  exerted  itself  nearly  always 
upon  patients  attacked  with  dilatation  of  the  stomach ;  it  had  even  attacked  four 
authentic  cases  of  relapse  of  typhoid  fever, — facts  certainly  very  rare  concerning 
the  subjects  of  dilatation.  He  draws  attention  to  the  relative  frequency  with  which 
we  meet  with  taenia  and  the  lumbrici  in  individuals  whose  stomach  is  imperfectly 
fulfilling  its  functions ;  which  shows  that  the  digestive  canal  of  the  subjects  of  dila- 
tation is  particularly  favorable  for  the  lodgment  of  disease-producing  parasites,  large 
or  small. 

M.  le  Gendre  finally  insists  upon  the  very  peculiar  frequency  with  which  we 
observe,  in  those  the  subjects  of  dilatation,  certain  morbid  conditions  badly  classed 
in  nosology, — afebrile  or  febrile  gastric  obstruction,  continued  febricula,  synocha ; 
choleriforni,  gastro-intestinal  catarrh, — many  of  which  are,  perhaps,  attenuated  forms 
of  typhoid  fever. 


LECTURE  XX. 

AUTO-lNTOXICATION   OF    INTESTINAL   ORIGIN — TYPHOID   FEVER. 

Part  played  by  auto-intoxication  in  typhoid  fever.  Typhoid  fever  is  caused  by 
an  infective  agent.  History  of  the  research  after  the  pathogenic  agent  of 
enteric  fever.  State  of  the  question.  My  own  researches.  The  infective 
nature  of  typhoid  fever,  although  not  absolutely  demonstrated,  is  probably 

absolute. Besides  the  general  infection  of  the  economy  by  the  pathogenic 

agent,  the  intestinal  ulce rations  are  a  cause  of  intoxication,  either  by 
increasing  normal  fermentations  or  by  the  induction  of  anomalous  fermenta- 
tive processes. Role  of  secondary  infections  arising  from  the  migration 

of  common  infective  agents  outside  of  the  intestine,  and  of  superadded 
infections,  by  penetration  into  the  debilitated  economy  of  special  pathogenic 

agents  :  parotiditis,  erysipelas,  gaseous  gangrene,  furuncle,  anthrax. Role 

of  increased  temperature  from  the  point  of  view  of  therapeutic  indication  of 
the  part  played  by  inanition.  Therapeusis  of  the  accidents  of  auto-intoxi- 
cation of  intestinal  origin  ;  disinfection  of  faecal  material  by  charcoal.  Anti- 
sepsis of  the  intestine  by  iodoform  and  naphthalin.  Part  played  by  purga- 
tives. Influence  of  intestinal  antisepsis  seen  in  the  diminution  of  mortality. 

THE  stucty  of  intoxication  of  intestinal  origin  does  not  appear 
to  lead  naturally  to  a  digression  upon  typhoid  fever.  This  is  an 
infectious  disease,  and  not  a  toxic  one,  and  j-et,  -when  we  come 
to  study  its  therapeutics,  it  is  necessary  to  deal  with  intoxica- 
tion. In  t3rphoid  fever,  in  short,  there  come  into  play  not  only 
the  minor  vegetable  organisms  which,  by  one  means  or  another, 
produce  all  the  disorders  which  an  infective  agent  can  cause. 
By  the  side  of  infection  there  is  evolved  a  secondary  process, — 
an  accessory  one, — which  is  subordinate  to  intoxication.  Well, 
then,  were  it  only  for  this  alone,  therapeutics  ought  to  concern 
itself  with  intoxication  in  typhoid  fever.  The  primary  cause  of 
abdominal  typhus  is  certainly  regarded  as  an  infective  agent, 
and  this  enters  by  the  intestinal  canal ;  all  that  we  know  of  its 
mode  of  transmission  authorizes  us  to  believe  this.  But  the 
infective  agent  only  exists  trausitionally  in  the  digestive  tube; 
that  is  not  its  habitat.  The  place  where  it  is  developed  is  the 
lymphatic  system, — the  closed  follicles,  Peyer's  glands,  mesen- 
teric  glands,  and  spleen.  It  may  be  eliminated  by  the  intestine, 
landing  there  at  the  moment  of  necrosis  of  Peyer's  patches,  and 
be  carried  away  by  alvine  discharges. 

(187) 


188  LECTURES   ON   AUTO-INTOXICATION. 

The  organism  which  may  be  the  infective  agent  of  enteric 
fever  has  been  known  for  a  long  time, — since  1811,  by  Reckling- 
hausen  ;  then  by  Klein,  Sokolof,  Browitz,  and  Fischl,  in  1878. 
I  have  myself  found  it,  in  1879,  and  I  communicated,  in  1880,  my 
researches.  I  have  found  it  in  all  the  pathological  liquids,  with 
the  exception  of  sudamina.  It  is  a  rod  possessed  of  the  power 
of  changing  its  form  frequently, — a  bacillus  one  day,  disposed, 
later  on,  in  the  form  of  beads,  then  as  isolated  micrococci.  We 
find  it,  at  the  autopsy,  in  certain  organs, — the  kidneys,  spleen, 
and  glands.  During  life,  I  have  found  it  in  the  urine;  this 
fact  was  a  novelty  at  that  period  ;  it  led  me  to  form  the  concep- 
tion of  infectious  nephrites.  I  have  said  that,  detected  in  the 
'blood  and  urine,  the  microbe  leaves  its  habitat  to  be  eliminated 
by  the  renal  emunctory.  This  fact  has  been  confirmed  since 
by  Letzerich,  who  saw  one  form  of  the  microbe, — the  coccus ; 
then  by  Eberth,  who  saw  it  in  the  form  of  a  rod  ;  and,  finally, 
by  Klebs,  Meyer,  Friedlander,  and  Gaffky.  But  does  this  fact, 
although  agreed  upon,  prove  that  the  microbe  is  the  pathogenic 
agent  of  typhoid  fever?  Certainly  not ;  it  is  necessaiy  that  we 
should  have  proved  its  presence  in  all  individuals  ;  that  we  should 
have  isolated  it  by  successive  cultures,  which  deprive  it,  by 
degrees,  of  all  that  has  been  borrowed  lay  it  from  the  patient  or 
the  cadaver  ;  and  that  in  inoculating  its  descendants  into  animals 
we  reproduce  in  them  the  disease  with  all  its  characteristics. 
Besides,  we  cannot  raise  objections  to  the  method  that  the 
organism,  even  isolated  and  cultivated,  has  not  caused  the 
disease.  Negative  results  do  not  prove  that  this  organism  may 
not  be  the  pathogenic  microbe.  Do  we  know  that  there  exists 
an  animal  species  liable  to  contract  typhoid  fever? 

In  every  case  the  result  of  inoculations  have  been  alwaj-s 
negative;  the  cultures  made  from  all  the  humors,  with  the 
exception  of  sudamina,  have  been  successful.  I  have  inoculated 
them  into  the  rabbit,  serpent,  cat,  dog,  and  pig,  and  I  have 
introduced  them  by  the  digestive  canal,  by  subcutaneous 
methods,  and  intra-venous  injection.  I  have  inoculated  quanti- 
ties of  the  culture  fluid  which  are  far  from  being  weak,  and 
which  certainly  contain  milliards  of  bacteria. 

I  have  readily  produced  in  the  pig  a  feverish  illness,  with 


TYPHOID   FEVER   AND   MICRO-ORGANISMS.  189 

evening  rise  of  temperature,  and  in  which  the  thermometric 
curve  is  broken  up  into  a  series  of  ascending  oscillations — a 
stadium  or  plateau — and  a  line  of  descending  oscillations.  Re- 
covery took  place  in  the  two  pigs  operated  upon.  Had  they  had 
a  bastard  typhoid  fever?  In  these  cases  I  ought  to  have  commu- 
nicated to  them  immunity  for  the  future.  Yet  fresh  intra-venous 
injections  of  typhoid  cultures  have  caused  in  them  renewed 
pyrexia  similar  to  the  first.  Typhoid  fever  being  a  disease 
which  creates  immunity,  the  anatomical  lesions  which  are  char- 
acteristic of  it  in  man,  not  having  been  established  in  other 
inoculated  pigs  which  have  not  recovered,  I  am  forced  to  admit 
that  the  disease  which  I  have  communicated  to  these  animals  is 
not  typhoid  fever.  Things  remain,  therefore,  at  the  point  in 
which  they  were  before  these  experiments,  and  I  have  no  right 
to  teach  that  typhoid  fever  is  a  parasitic  disease,  like  anthrax  or 
glanders. 

Thus  we  have  had,  so  far  as  the  subject  of  the  infectious 
nature  of  typhoid  fever  is  concerned,  only  probabilities.  An 
important  argument  is  that  typhoid  fever  is  transmissible, — con- 
tagious. As  a  general  rule,  we  do  find  a  relationship  between 
cases.  A  patient  who  has  come  to  a  district  becomes  a  centre 
from  which  radiate  other  patients,  who  scatter  the  disease  in  the 
healthy  localities.  Transmission  especially  occurs,  as  we  know, 
by  the  dejecta,  and  mediately  through  the  drinking-water  which 
the  dejecta  have  impregnated.  Thus  it  is  that,  calculating  upon 
clinical  and  etiological  facts,  and  not  upon  microscopic,  we 
have  come  to  regard  typhoid  fever  as  the  result  of  the  introduc- 
tion of  a  parasitic  agent  into  the  organism.  But,  besides 
general  infection,  the  disease  induces  local  effects.  The  most 
remarkable  are  the  intestinal  lesions,  consisting  in  ulceration  and 
in  gangrene  of  certain  parts  of  the  intestine,  then  in  excessive 
putrefactions,  which  are  in  this  way  developed,  showing  them- 
selves by  meteorism  and  a  fetid  diarrhoea.  I  do  not  say  that 
these  putrefactions  arise  from  the  presence  of  a  pathogenic 
organism,  but  we  have  reason  to  believe  that  it  operates  upon 
the  normal  excessive  fermentations  in  the  intestine,  besides  the 
anomalous  fermentative  processes  of  which  the  organs  are  the 
seat. 


190  LECTURES   ON   AUTO-INTOXICATION. 

If  the  fecal  matter  of  a  man  in  health  is  toxic,  in  typhoid 
fever  the  unusual  intensity  of  normal  putrefaction  may  easily 
add  something  to  the  infection,  and  we  may  conceive  how,  from 
such  a  source,  there  must  be  some  notice  taken  of  intoxication 
in  the  treatment.  We -must  deal,  too,  with  the  secondary  infec- 
tions arising  from  the  migration  of  ordinary  infectious  agents 
from  the  intestine  and  from  the  surface  of  intestinal  wounds  into 
the  blood  and  the  tissues,  where  their  multiplication  is  favored 
by  want  of  resistance  of  the  latter.  It  is  probably  these  common 
infectious  agents,  on  the  move,  which  cause  certain  forms  of 
abscess,  furunculosis,  anthrax,  and  externally  ordinary  eschars  ; 
in  parts  of  the  body  which  are  not  subjected  to  pressure, 
certain  spontaneous  forms  of  gangrene  arise,  perhaps  from  the 
action  of  common  infective  agents  upon  the  tissues,  where  their 
influence  for  harm  is  no  longer  counter-balanced  by  the  activity 
of  the  circulation  and  nervous  system. 

We  sometimes  see,  in  the  course  of  typhoid  fever,  certain 
infective  processes  superadded,  such  as  parotiditis.  Inflamma- 
tion of  the  parotid  is  produced  by  ordinary  infective  agents, 
which  are  introduced  by  the  excretory  salivary  ducts;  and  this 
occurs  as  much  by  other  glands, — e.gr.,  by  the  kidney  when  it  is 
no  longer  in  function,  and  when  the  bladder  is  the  seat  of  in- 
flammation (miliary  abscess ;  surgical  kidney). 

Erysipelas  is  frequent  in  the  advanced  periods  of  typhoid 
fever.  We  may  even  see  it  cause  gaseous  gangrene.  In  certain 
cases  the  eschars  from  the  decubitus  of  the  patient  are  the  point 
of  departure  of  an  emphysema  which  extends  some  distance.  I 
have  seen  a  case  in  which  gaseous  gangrene  has  been  the  cause  of 
death.  It  is  not  simply  enough  to  conceive  of  typhoid  fever  as  the 
result  of  a  general  infection  by  putrid  intoxication  derived  from 
the  digestive  tube,  or  of  secondary  infection,  and  of  superadded 
infection ;  we  must  consider  it  along  with  one  of  its  necessary 
effects, — the  fever.  It  is  impossible  to  build  up  a  systematic 
treatment  upon  one  pathogenic  view  onhr.  Doubtless,  if  we 
could  at  once  destroy  the  pathogenic  agent,  this  great  blow 
would  be  decisive  and  would  put  an  end  to  the  fever,  as  also  to 
all  the  fatal  accidents.  But,  since  we  cannot  attain  this  end,  we 
must,  I  repeat,  reckon  with  the  fever,  and,  if  this  becomes  of 
itself  dangerous,  try  to  reduce  it. 


ANOMALOUS   SYMPTOMS   IN   TYPHOID   FEVEE.  191 

We  are  here  in  the  presence  of  a  continued  fever, — which  is, 
without  intermission, destroying  the  patient  for  weeks, — which  is 
higher  than  39°  C.  (102.2°  F.),  which  brings  about  unusual  meta- 
morphoses in  living  matter,  depriving  it  of  oxygen  ;  induces 
modifications  which  are  subversive  of  nutrition  and  perversive 
of  disassimilation.  This  excessive  temperature  produces  effects 
which  are  harmful  to  muscular  fibre  and  the  nervous  system. 
Sometimes  the  patients  die  simply  from  the  persistent  hvper- 
thermia.  The  physician  has  not,  therefore,  only  to  deal  with 
the  cause  of  the  disease.  When  he  cannot  suppress  that,  he 
ought  to  struggle  in  succession  against  all  the  effects  arising 
from  this  cause. 

During  the  long  course  of  this  fever,  inanition  is  extreme. 
The  patient,  taking  no  combustible  material  from  the  outer 
world,  lives  upon  his  own  tissues.  He  finds  that  it  is  impossible 
for  him  to  digest.  We  cannot,  therefore,  nourish  him  like 
another  person ;  still,  we  should  try,  by  ingenious  means,  to 
introduce  into  his  organism  combustible  material,  and  not  allow 
him  to  destroy  his  own  tissues. 

As  many  as  are  the  indications  to  be  fulfilled  in  the  treat- 
ment of  typhoid  fever,  just  as  many  are  the  difficulties  to  be 
overcome.  We  must,  so  to  speak,  lay  siege  to  the  disease  and 
attack  it  at  all  points  where  it  appears  vulnerable.  Yet  I  have 
only  laid  down  general  indications ;  there  are  still  special 
indications  for  such  and  such  a  disease,  such  and  such  a 
particular  accident. 

I  now  come  to  the  therapeusis  of  the  accidents  of  intoxica- 
tion of  intestinal  origin.  In  the  last  ten  years  I  have  been 
giving  charcoal  to  neutralize  a  part  of  the  toxic  products.  More 
recently,  I  have  completed  this  method  by  the  addition  of  means 
to  prevent  the  fermentations  which  develop  toxic  products.  I 
will  tell  you  some  results  which  I  have  obtained  in  these  two 
phases  of  my  practice  : — 

With  charcoal  I  have  deodorized  and  discolored  completely 
faecal  matter;  I  diminished  their  toxicit}',  and  the  alkaloids 
found  are  no  longer  but  in  insignificant  quantity  in  the  filtered 
liquid.  These  first  effects  some  have  denied.  It  has  been  said, 
in  one  of  the  learned  societies,  that  charcoal  was  not  an  anti- 


192  LECTURES  ON   AUTO-INTOXICATION. 

septic  substance,  without  it  being  known  for  what  reason  I  was 
employing  it.  Besides,  it  has  been  stated,  too,  that  charcoal  does 
not  succeed  in  disinfecting ;  yet  we  have  had  proof  of  all  that 
I  have  said,  by  giving  2  grammes  of  charcoal  in  medicated 
cachets.  As  for  myself,  who  gave  100  grammes  daily,  spoonfuls 
by  the  mouth  every  two  hours,  I  have  obtained  liquid  stools, — 
black,  odorless,  and  not  resembling  fascal  matter.  Such  matter 
has  not  only  optical  and  olfactory  properties  which  are  less  dis- 
agreeable, but  intra-venous  injections  show  that  they  are  much 
less  toxic ;  their  toxicity  is  found  reduced  by  four-fifths.  Not 
only  is  the  matter  contained  in  the  intestine  less  toxic,  but  a 
consequence  easjr  of  demonstration  is  that  the  individual  is  not 
poisoned,  for  the  toxicity  of  his  urine  is  found  considerably 
diminished.  The  urine  remains  toxic  owing  to  the  products  of 
alimentation  or  of  disassimilation,  but  they  are  no  longer  convul- 
sive. We  must  employ  from  90  to  120  cubic  centimetres  of 
urine  in  order  to  kill  1  kilogramme  of  animal. 

Owing  to  the  disinfection  of  the  stools,  we  also  obtain 
other  beneficial  results.  The  patients  have  no  longer  the  earthy 
complexion,  but  a  clear  skin,  white  and  red;  the  intestinal  dis- 
tension diminishes;  the  tongue  remains  moist;  eschars  are 
extremely  rare. 

Finally,  statistics  resting  upon  more  than  300  cases  have 
shown  that  the  mortality  had  fallen  to  15  per  cent.,  instead  of  20 
to  25  per  cent.  In  these  statistics  I  include  all  the  cases,  with- 
out exception,  which  have  come  under  my  hospital  care  :  the 
patients  who  have  not  been  submitted  to  this  treatment,  those 
who  have  come  with  an  intestinal  perforation,  or  have  succumbed 
to  slow  complications.  I  would  be  perfectly  right  in  deducting 
all  these  patients,  in  order  to  judge  of  the  value  of  the  treatment 
by  itself;  but  I  have  not  done  so  in  order  to  establish  a  compari- 
son with  other  methods.  I  take  the  total  mortality,  en  bloc,  of 
the  hospitals  of  Paris. 

For  the  last  two  years  I  have  added,  to  disinfection,  intestinal 
antisepsis.  After  numerous  attempts,  after  having  employed 
creasotelike  Pecholier,  salicylic  acid,  and  mercurial  preparations, 
I  have  returned  to  the  true  principles  of  intestinal  antisepsis  by- 
applying  substances  capable  of  acting  throughout  the  whole 


MEANS   EMPLOYED   TO   INDUCE   INTESTINAL   ASEPSIS.  193 

length  of  the  digestive  canal;  that  is,  insoluble  substances, — the 
stilicylate  of  bismuth,  iodoform,  naphthalin.  I  have  onl}7  em- 
ployed pheuic  acid  to  wash  out  the  large  intestine,  morning  and 
evening.  I  have  caused  to  be  given  a  carbolic  enema  of  1  in  1000, 
except  in  the  case  of  infants,  where  this  sometimes  causes  a 
collapse  rather  disquieting  in  appearance  ;  in  the  adult,  even,  one 
has  seen  perspiration,  faintness,  almost  coma.  With  the  doses 
to  which  I  have  alluded,  these  accidents  are  very  rare;  they 
may  be  such  as  to  cause  a  little  fear,  but  they  are  not  grave. 

I  cause  to  be  taken  daily  by  my  typhoid  patients  1  gramme 
of  iodoform,  finely  powdered  and  representing  a  surface  of  60 
square  metres.  I  obtain,  by  this  method,  as  the  fecal  matters 
are  deodorized  and  discolored,  a  diminution  of  the  alkaloids 
which  the  filtered  liquid  contains,  a  diminution  of  the  toxicity 
of  the  fsecal  matter,  the  almost  complete  disappearance  of  the 
agents  of  putrefaction.  Microbes  are  no  longer  found  in  the 
alvine  secretions,  save  in  very  minute  quantity.  The  tongue  of 
the  patient  is  never  diy. 

The  mortality  in  the  same  hospital,  in  the  same  quarter,  with 
the  same  physician,  has  fallen  to  10  per  cent., — an  index  at  once 
consoling.  The  partisans  of  the  cold-bath  treatment  are  proud 
enough  with  this  index  of  10  per  cent.,  but  I  have  reached  it 
without  baths. 

I  have  taken  care  to  add  to  the  preceding  methods  a  purga- 
tive every  three  days, — a  glassful  of  Seidlitz  water, — and  I  never 
abandon  the  treatment  without  subsequently  causing  a  clearing 
out  of  the  intestine  by  a  purgative.  Otherwise,  there  may  be 
produced  in  the  large  intestine  a  hard  accumulation,  capable  of 
causing  alarming  obstruction,  with  faecal  vomiting.  This  pur- 
gative is  castor-oil,  administered  to  the  patient  in  a  small  dose, 
whilst  he  is  in  a  bath. 

Such,  then,  are  the  principles  of  the  antiseptic  method 
applied  to  the  digestive  tube  of  patients  attacked  with  typhoid 
fever.  For  one  year  I  combined  naphthalin  with  iodoform;  the 
time  has  not  yet  arrived  for  me  to  be  able  to  judge  of  the  value 
of  this  new  method  of  medicinal  treatment. 


LECTURE  XXI. 

PATHOGENIC  THERAPEUSIS  OF  TYPHOID  FEVER — ANTISEPSIS  OP  THE 
INTERNAL  MEDIUM. 

Is  general  antiseptic  medication  theoretically  admissible  ?  Can  we  destroy  in- 
fectious agents  in  the  economy  ?  Antisepsis  of  the  internal  medium.  Refu- 
tation of  objections. Substances  capable  of  preventing  the  multiplica- 
tion of  infectious  agents  that  are  vegetable  are  not  necessarily  fatal  to 
animal  cells :  the  aspergillus,  for  example.  The  antiseptic  action  of 
medicaments  is  not  paralleled  by  their  toxic  power.  Therapeutic  and  anti- 
septic equivalents. Antisepsis  is  proposed  not  so  much  in  order  to  de- 
stroy microbes  as  to  prevent  their  reproduction.  A  simple  change  of  the 
medium  is  sufficient  to  cause  large  vegetables  to  become  sterile. Expe- 
rience has  demonstrated  the  utility  of  employing  antiseptic  medicaments. 
Specific  medicaments  are  all  antiseptic.  Mercury.  Quinine.  Salicylic 
acid.  Phenic  acid.  The  largest  number  of  medicaments  called  antipyretics 
act,  perhaps,  only  as  antiseptics. Attempts  at  producing  general  anti- 
sepsis in  typhoid  fever.  Mercury  may,  perhaps,  shorten  the  duration  of 
typhoid  fever.  Its  inconveniences  as  the  exclusive  method. 

I  CONTINUE  the  study  of  the  therapeutic  indications  in 
typhoid  fever.  Beyond  internal  antisepsis,  of  which  I  have 
shown  to  you  by  statistics  the  incontestable  advantages,  is  there 
not  something  to  do  from  the  point  of  view  of  real  general  anti- 
sepsis? Is  there  a  therapeusis  rigidly  pathogenic  of  typhoid 
infection?  This  disease  may  serve  as  an  example  to  us  more 
than  any  other  in  order  that  we  may  judge  of  certain  questions 
of  general  therapeusis.  Apropos  of  it,  we  may  study  the  prin- 
ciples of  the  antiseptic  method,  of  the  antipyretic  method,  and 
the  rules  which  should  regulate  the  feeding  of  patients  in 
infectious  febrile  diseases. 

I  am  anxious  to  declare  that  I  do  not  substitute  the  anti- 
septic method  for  the  antipyretic  in  the  treatment  of  typhoid 
fever,  and  that  I  have  not  the  desire  to  suppress  all  that  has 
been  done  in  the  way  of  antipyretic  medication,  in  order  to 
attempt  to  substitute,  for  real  and  serviceable  results,  that  which 
is  still  hypothetical  and  irregular  in  its  effects. 

But  if  it  is  good  to  attack  hyperthermia,  which  is  a  source 
of  continual  danger  in  fevers,  it  is  permissible  to  attack  it  in  its 
(194) 


ANTISEPSIS  OF   THE   INTERNAL   MEDIUM.  195 

origin  ;  and  in  those  maladies  whose  cause  is  the  penetration  of 
vegetable  organisms  into  the  system,  does  it  not  become  us  to 
seek  for  that  which  we  ourselves  can  oppose  to  their  presence 
and  multiplication?  Can  we,  definitely,  in  infectious  diseases, 
effectually  attack  the  infective  agent? 

Some  have  denied  that  this  is  possible.  And  yet  the  ques- 
tion has  been  settled  in  the  affirmative  by  surgery.  We  can  no 
longer  discuss  here  the  possibility  of  suppressing  septic  agents. 
We  are  now  dealing  with  infection  of  free  or  unbroken  surfaces, 
on  which  infectious  agents  multiply;  on  which  are  accumulated 
toxic  substances, — infective  agents  which  may  proceed  to  form 
colonies  in  various  organs,  and  poisons  which  may  cause  else- 
where secondary  functional  derangement.  It  is,  besides,  through 
the  imitation  of  that  which  surgeons  have  obtained  that  I  have 
demonstrated  the  possibility  of  effecting  intestinal  antisepsis. 
In  medicine,  we  can  still  quote  the  example  of  certain  diph- 
therias which  remain  for  a  time  infectious  on  the  surface,  and  to 
which  antisepsis  of  the  surface  is  applicable. 

When  we  are  dealing  with  patients  in  whom  the  infection  is 
no  longer  on  the  surface,  but  one  of  general  infection,  things  are 
presented,  it  is  true,  under  another  light.  Sometimes  it  is  the 
blood  which  may  be  the  natural  habitat  of  the  infectious  agents, 
as  in  anthrax  and  relapsing  fever.  Sometimes  the  pathogenic 
agents  are  localized  in  the  tissues.  In  every  case,  one  must 
succeed  in  impregnating  the  whole  organism  with  the  antiseptic 
agent. 

But  do  we  not  injure,  at  the  same  time,  the  animal  cells? 
This  objection,  which  appeals  to  sense,  has  been  from  the  first 
the  principal  reason  why  the  opponents  of  antiseptic  medication 
have  never  supported  it.  It  has  been  formulated  in  a  startling 
manner  when  it  has  been  said,  "  We  aim  at  the  microbe  and  we 
strike  the  patient."  Nevertheless,  this  masterly  expression,  for 
which  I  entertain  respectful  esteem,  is,  at  the  bottom,  only  a 
sophism.  We  can  answer,  actually,  that  what  is  hurtful  to  one 
vegetable  cell  is  not  always  hurtful  to  another  cell  of  an  animal 
nature.  Thus,  is  there  not  a  whole  series  of  pathogenic  agents 
which  are  killed  by  a  substance  indispensable  to  the  animal,  viz., 
oxygen  (they  are,  unfortunately,  not  the  most  numerous)  ?  We 


196  LECTURES   ON   AUTO-INTOXICATION. 

cannot,  therefore,  say  that  what  will  kill  the  microbe  will  neces- 
sarily destroy  the  patient.  We  can,  besides,  support  the  argu- 
ment by  the  experiment  of  Raulin,  who  has  shown  that  silver,  in 
an  almost  infinitesimal  dose,  is  opposed  to  the  development  of 
the  aspergillus.  Here,  then,  is  a  substance  fatal  to  certain 
vegetable  cells  in  a  dose  not  at  all  hurtful  to  animal  cells.  On 
the  contraiy,  certain  inferior  vegtables  live  preferably  in  media 
poisonous  to  the  animal  (solutions  of  quinine,  arsenic,  and  anti- 
mony in  doses  fatal  to  man).  We  must,  therefore,  separate  off 
antiseptic  substances  so  as  to  state  precisely  those  which  are 
very  hurtful  to  vegetable  cells,  and  yet  innocent  so  far  as  the 
elementaiy  tissues  of  the  animal  are  concerned. 

The  antiseptic  action  of  medicaments  does  not  proceed  in  a 
parallel  manner  with  their  toxic  power.  Bert  was  wrong  in 
identifying  the  nerve  cell  with  the  cell  of  the  ferment.  To 
say  that  what  is  hurtful  to  a  vegetable  cell  ought  to  injure,  a  for- 
tiori, a  nerve  cell,  is  only  true  for  certain  cases  and  in  certain 
conditions.  Aniline  is  toxic  and  antiseptic.  Phenic  acid  is 
equally  toxic  and  antiseptic.  But  is  there  an}r  parallelism  be- 
tween their  toxicity  and  their  antiseptic  power?  Aniline  is  five 
times  less  antiseptic  than  phenic  acid,  but  four  times  more  toxic 
for  animal  cells. 

Can  we  compare,  from  the  same  points  of  view,  phenic  acid  with 
mercury?  With  the  same  toxic  power,  phenic  acid  is  six  times 
less  antiseptic  than  the  salts  of  mercury.  The  choice  of  these 
second  substances  is  imposed  upon  us,  therefore,  when  we  wish 
to  obtain  maximum  action  against  microbes  and  the  least  against 
the  animal  elements. 

Amongst  mercurial  salts,  all  have  not  an  antiseptic  action 
proportionate  to  their  toxicity.  The  biniodide,  eminently  anti- 
septic, is  less  toxic  than  an  equal  weight  of  the  bichloride. 

The  iodides  of  potassium  and  sodium  are  moderately  anti- 
septic. To  prevent  the  fermentation  of  a  litre  of  soup,  we  must 
add  to  it  48  grammes  of  iodide  of  potassium  or  50  grammes  of 
iodide  of  sodium.  The  action  that  is  hurtful  to  the  ferment  is 
then  sensibly  the  same  for  these  two  bodies,  but  the  iodide  of 
sodium  is  forty  times  less  hurtful  to  the  animal  than  iodide  of 
potassium. 


ANTISEPSIS   TO   PREVENT   REPRODUCTION   OP   MICROBES.          197 

It  is  advisable,  therefore,  to  compare  therapeutic  equivalents 
of  medicaments  and  their  antiseptic  equivalents.  We  can  also 
derive  benefit  from  the  combination  of  different  antiseptic  sub- 
stances. If  we  wish  to  administer,  simultaneously,  two  or  three 
antiseptics,  it  seems  that  we  must — in  order  not  to  run  the 
risk  of  causing  intoxication — not  give  any  one  of  these  bodies 
in  more  than  one-half  or  one-third  of  the  dose  which  is  the 
limit  of  their  toxicity.  I  have  observed  that  we  can  go  beyond 
these  fractions.  In  choosing  antiseptics  and  in  associating 
them,  we  can  double  the  antiseptic  power  and  only  increase 
by  one-third  their  toxic  activity.  Such  a  vegetable  organism  is 
not  otherwise  influenced  by  an  antiseptic  agent  which  kills  other 
vegetables.  There  is  room,  therefore,  for  fresh  experiments  ;  but 
it  is  advisable  to  follow  these  therapeutic  attempts,  relying  at  first 
upon  the  experimental  method  amongst  animals. 

I  have  tried  to  make  experiments  with  antiseptics  upon  the 
infective  agent  of  typhoid  fever,  or  at  least  upon  its  assumed 
pathogenic  agent  whose  culture  is  easy  in  the  neutral  soup  made 
from  beef;  its  sensibility  is  greater  to  the  action  of  biniodide  of 
mercurv  than  is  that  of  the  bacterium  of  fermenting  soup, — a 
long  bacterium  whose  sensibility  is  as  2,  that  of  the  typhogenetic 
agent  being  3.  Finally,  as  a  last  argument,  it  is  said  in  objection 
that  we  cannot  kill  pathogenic  bacteria  without  destroying  the 
cells  of  the  patient.  But  what  we  propose  is  not  so  much  to 
bring  about  death  of  the  microbes  in  the  depths  of  the  organism 
as  to  prevent  their  multiplication.  It  is  one  thing  to  destroy  an 
individual  and  another  to  render  him  sterile.  I  borrow  a  con- 
vincing example  from  botany.  A  palm-tree  from  Biskra,  which 
covers  itself  with  fruits  destined  to  ripen  when  it  grows  to  the 
limit  it  would  have  attained  in  the  desert,  can  live  quite  well  in 
the  greenhouses  of  the  museum,  but  it  will  never  develop  within 
them  fruit  capable  of  reproducing  itself;  it  will  not  even  bear 
fruit  in  Algeria.  Thus,  a  simple  modification  of  the  medium, 
whilst  leaving  to  vegetable  organisms  their  vital  integrity  ami 
all  their  energy,  can  render  them  incapable  of  multiplication. 
The  liquid  of  a  malignant-pustule  culture  inoculated  into  sheep 
belonging  to  Beauce  will  cause  death  in  all  of  them,  but  if  sheep 
of  the  same  breed  are  taken  to  Algeria,  and  are  inoculated  with  the 


198  LECTURES  ON   AUTO-INTOXICATION. 

same  culture,  nineteen  inoculations  out  of  twenty  will  remain 
sterile.  What  is  true  with  regard  to  large  vegetables  is  also  true 
of  the  smaller.  If  we  pass  to  the  application  of  this  idea  of  re- 
production, it  is  perfectly  immaterial  whether  man  is  rendered 
incapable  of  multiplying  cells  during  his  illness  ;  but  if  we 
can  prevent  the  cells  of  his  parasite  from  being  multiplied,  the 
disease  ceases,  for  it  is  not  caused  only  by  the  presence  and 
development  of  the  ferment,  but  by  its  multiplication.  Let  us 
propose  to  ourselves  only  to  oppose  the  latter,  and  let  us  merely 
try  to  impede  the  activity  of  this  multiplication. 

En  r&sume,  general  antisepsis  is  theoretically  admissible,  and 
we  have  no  right  to  refuse  its  admission  by  an  a  priori  exception. 
What  it  requires  now  is  not  argument;  facts  are  necessary  to 
establish,  and  that  thoroughly,  the  employment  of  antiseptics 
which  have  impeded  the  course  of  certain  infectious  diseases. 

Well,  has  experience  not  already  produced  an  opinion  ?  Is 
syphilis  cured  by  the  antiplastic  virtue  of  mercury  ?  We  can 
scarcely  maintain  that  to-day.  In  intermittent  fever,  is  it  as  an 
antithermic  that  sulphate  of  quinine  brings  about  a  cure ;  and 
in  rheumatism,  salicylic  acid? 

Quinine  brings  about  a  reduction  of  temperature  in  an  im- 
portant and  useful  manner  in  three  diseases  only, — intermittent 
fever,  typhoid  fever,  and  one  of  the  forms  of  puerperal  fever. 
In  a  healthy  man  it  increases  it  l>y  some  tenths  of  a  degree;  it 
does  not  reduce  it  in  other  febrile  diseases.  In  fibrinous  lob:vr 
pneumonia  3  to  4  grammes  of  quinine  produce  quinism  without 
reducing  the  temperature  more  than  one-half  a  degree.  In  the 
subject  of  pleurisy  the  effect  is  not  more  marked.  In  erysipe- 
las you  do  not  reduce  the  temperature  even  with  large  doses 
of  quinine.  In  the  diseases  in  which  quinine  acts,  it  is  only  by 
acting  in  opposition  to  the  infective  agent  that  it  causes  a 
cessation  of  the  fever  which  is  the  consequence  of  it. 

It  is  not  so  with  phenic  acid.  Plienic  acid  reduces  tempera- 
ture by  its  physiological  properties ;  by  its  action  on  animal 
cells  it  diminishes  calorification  and  also  acts  upon  the  vegetable 
cells  of  infectious  organisms. 

An  enema  containing  48  grammes  of  crystallized  phenic  acid 
was  administered  to  two  of  my  patients,  at  intervals  of  two 


SPECIFIC   MEDICAMENTS   ALL   ANTISEPTIC.  199 

minutes  between  each  injection.  The  mistake  was  made  by 
attendants  who  were  new  to  the  work.  The  first  patient  uttered 
loud  cries  while  the  solution  was  being  administered  to  the 
second.  The  nurse,  being  alarmed,  ran  for  the  house-surgeon, 
who  ordered  the  bowels  to  be  immediately  washed  out  with  15 
litres  of  water.  The  patients  were  already  in  a  state  of  coma, 
in  which  they  remained  for  several  hours,  their  temperature  being 
35°  C.  (95°  F.).  One  of  them  had  a  temperature  of  40°  C. 
(104°  F.)  before  this  accident,  the  other  was  convalescent;  the 
first  rose  to  41.8°  C.  (107.4°  F.)  in  the  evening,  and  in  the  same 
time  the  other  reached  exactly  the  same  temperature ;  the  one 
that  had  a  temperature  of  40°  C.  (104°  F.)  was  apyretic  the  next 
day  with  a  temperature  of  37°  C.  (98.6°  F.),  and  remained  con- 
valescent; the  disease  was  destroyed,  but  the  patient  was  nearly 
killed  as  well.  This  is  also  true  of  alcohol ;  I  observed  it  in  the 
case  of  a  young  woman  who  had  caught  tj'phoid  fever  in  Rome. 
She  was  having  injections  of  1  in  1000  of  phenic  acid.  The 
Sister  of  Mercy,  by  mistake,  one  day  administered  an  enema 
with  alcohol  at  80°  C.  (176°  F.).  Her  malady  had  reached  the 
ninth  day ;  the  first  lenticular  red  spots  were  appearing.  Her 
temperature  fell  to  35°  C.  (95°  F.)  ;  she  was  delirious  and  totally 
blind.  When  the  temperature  once  returned  to  37°  C.  (98.6°  F.), 
it  remained  at  this  point  for  four  days.  The  maladj"  resumed 
its  course ;  the  microbes  had  merely  been  dormant ;  they  required 
a  certain  time  to  reproduce  the  pyretic  symptoms. 

Almost  all  the  drugs  that  reduce  fever  in  typhoid  fever  are 
antiseptic.  All  those  that  are  reputed  specifics  or  nro  generally 
considered  useful  are  antiseptic  :  chlorine,  iodine,  sulphurous  acid, 
the  sulphites  and  hyposulphites,  the  mercurials,  essence  of  tere- 
binthine,  creasote,  thymic  acid,benzoic  acid,  salicylic  acid,  boric 
acid,  iodoform,  quinine,  resorcin,  kairin,  antipyrin,  thallin.  I 
think,  therefore,  that  experience  confirms  the  general  opinion 
as  to  their  usefulness,  and  that,  practically  as  well  as  theoreti- 
cally, a  favorable  effect  may  be  obtained  in  the  course  of  in- 
fectious diseases  by  the  employment  of  the  above-named 
substances.  Of  these,  one  especially  lias  been  considered  a  spe- 
cific, viz.,  mercury.  It  is  long  since  calomel  has  been  admin- 
istered in  large  doses,  or  the  black  sulphide.  Mercurial  friction 


200  LECTURES  ON   AUTO-INTOXICATION. 

was  used  by  Serres,  and  by  Becquerel,  until  salivation  and  ulcer- 
ation  of  the  mouth  were  produced.  Since  that  time  calomel 
has  been  recognized  as  a  valuable  agent  in  German}-  and  Eng- 
land, and  in  France  by  M.  Salet,  of  Saint-Germain.  He  recom- 
mends a  method  which  consists  in  administering  1  centigramme 
of  calomel  every  hour  until  salivation  ensues.  At  this  juncture 
the  illness  takes  a  turn  one  way  or  another. 

This  mode  of  treatment  being  supported  by  a  considerable 
number  of  facts,  I  determined  to  verify  the  results.  I  gave  thirty- 
two  patients  who  were  suffering  from  typhoid  fever  40  centi- 
grammes of  calomel  a  day,  in  doses  of  2  centigrammes  every 
hour,  until  mercurial  salivation  was  produced.*  In  almost  every 
case  this  took  place  in  from  five  to  seven  days.  All  the  patients 
that  experienced  this  salivation  recovered.  The  mean  duration 
of  the  malady  was  twenty  one  days, — a  short  period,  twenty-five 
days  being  the  usual  duration.  The  mortality  was  low  ;  two  out  of 
thirty-two  died,  or  6  per  cent.  Certainly,  the  number  of  cases  was 
too  small  to  enable  us  to  arrive  at  any  definite  conclusions.  I 
may  merety  mention  that  those  who  died  were  those  who  had  taken 
the  least  mercury,  and  were  consequently  not  sufficiently  under 
its  influence.  The  recoveries  in  less  than  twenty -one  days  were 
twice  more  numerous  than  by  the  other  method. 

But  I  did  not  continue  this  treatment,  although  the  patients 
recovered  more  quickly,  and  seemed  to  recover  more  com- 
pletely, as  it  has  the  disadvantages  of  causing  a  long  period  of 
convalescence,  great  debility,  and  anaemia.  Certain  accidents, 
too,  seemed  to  me  more  frequent :  epistaxis ;  intestinal  haemor- 
rhage ;  dysenteric,  sanguinolent,  and  mucous  stools.  Other 
patients  suffered  from  later  complications, — pneumonia  twelve 
days  after  recovery  from  the  original  malady  and  a  vegetative 
endocarditis.  However,  although  I  rejected  this  method  as  an 
exclusive  mode  of  treatment,  I  thought  it  might  be  used  with 
advantage  if  the  system  were  less  completely  impregnated  with 
the  drug.  I  adopted  it,  therefore,  at  the  commencement  of  the 
illness  only,  and  associated  it  with  other  therapeutic  agents, 
under  the  form  of  a  mixed  system  of  treatment,  which  I  shall 
describe  in  detail  hereafter. 

*  40  centigrammes  equal  6.2  grains ;  2  centigrammes  equal  0.31  grain. 


LECTURE    XXII. 

ON   THE    PATHOGENIC    THERAPEUTICS   OF   TYPHOID  FEVER— THE 
TREATMENT  OP  HIGH  TEMPERATURE. 

The  use  of  calomel  in  minute  doses  as  a  general  antiseptic  agent. Conse- 
quences of  excessive  temperature  in  infectious  diseases.  The  effects  of  high 
temperature  obtained  by  experiment.  The  effects  of  high  temperature  as 

regards  denutrition. Excessive  temperature  indicates  the  gravity  of  the 

disease,  but  does  not  cause  it.     It  is,  however,  advisable  to  endeavor  to 

reduce  it.     Methods  of  lowering  it. Sources  of  abnormal  heat.    Causes  of 

the  rise  of  temperature  in  febrile  maladies. The  effects  of  antitherrriic 

drugs  and  modes  of  treatment. 

I  HAVE  described  under  four  headings  the  therapeutics  of 
typhoid  fever:  the  general  antiseptic  treatment,  the  intestinal 
antiseptic  treatment,  the  antipyretic  medicinal  treatment,, and 
the  dietetics  of  food  and  drink. 

I  have  described  at  some  length,  in  speaking  of  chronic 
intoxications  of  intestinal  origin,  how  I  proceed  with  the  intes- 
tinal antiseptic  treatment ;  in  my  last  lecture  I  gave  my  reasons 
for  rejecting  the  general  antiseptic  treatment  by  the  exclusive 
use  of  mercurial  salts,  at  the  same  time  admitting  the  specific 
action  of  mercury.  Thus,  I  employ  part  of  the  general  anti- 
septic method  in  combination  with  other  modes  of  treatment. 

I  use  calomel  in  minute  doses  at  the  outset,  and  until  the 
commencement  of  the  second  week.  I  administer  each  day 
40  centigrammes  of  calomel,  divided  into  20  doses  which  a  re- 
taken every  hour,  without  either  trying  to  produce  or  obtaining 
salivation.  This  treatment  is  continued  for  four  consecutive 
days.  Generally  speaking,  it  has  seemed  to  me  that  the  thermic 
curve  was  modified,  and  that  sometimes  after  the  second  day  the 
fever  began  to  abate,  varj'ing,  at  the  end  of  four  days,  liciwcrn 
39°  C.  (102.2°  F.)  and  40°  C.  (104°  F.),at  a  period  when  in  the 
ordinary  course  of  the  malady  the  temperature  would  either  be 
rising  or  remaining  stationary.  I  do  not  wish  to  produce  and  I 
never  obtain  salivation. 

I  will  now  proceed  to  discuss  those  antipyretic  or  antithermic 
drugs  that  are  in  great  favor  at  the  present  day.  There  is  a 

(201) 


202  LECTURES   ON   AUTO-INTOXICATION. 

certain  school  of  medicine  that  sees  nothing  in  fevers  but  fever; 
with  doctors  of  this  class  the  thermometer  is  the  source  of  all 
therapeutic  and  prognostic  indications  ;  they  see  improvement 
only  in  lowering  of  the  temperature.  No  clinical  practitioner 
can  accept  such  a  doctrine,  and  the  audacity  of  the  assertions 
of  the  school  in  question  has  given  rise  to  a  reaction  in  the  con- 
trary direction,  in  Germany  as  well  as  in  France.  Thus  we  now 
see  the  current  of  medical  opinion  take  a  new  course.  It  is 
now  urged  that  fever  may  do  some  good,  and  that  it  should  be 
treated  with  respect, — a  theory  that  has  long  been  unheard  of  in 
the  medical  world.  This  is  a  return  to  the  Hippocratic  and  tra- 
ditional doctrine,  which  I  have  supported  as  regards  diseases  of 
nutrition. 

I  have  dwelt  upon  the  theory  that  there  are  fevers  which,  at 
certain  times,  re-establish  equilibrium  in  exhausted  nutrition  by 
bringing  about  interstitial  metamorphoses.  This  is  evident  in 
gout.  But  is  it  also  true  of  infectious  diseases?  Can  fever 
help  the  system  to  free  itself  from  the  infectious  organism  ?  We 
know  that  certain  microbes  cannot  live  beyond  certain  tempera- 
tures which  do  not  kill  a  human  being.  The  bacteria  of  malig- 
nant pustule,  which  cannot  live  in  a  temperature  higher  than 
40°  C.  (104°  F.),  have  no  effect  on  birds,  their  normal  tem- 
perature being  above  that  point.  Pasteur  has  shown  that  it  is 
necessary  to  cool  a  fowl,  in  order  to  render  it  able  to  contract 
this  disease.  This  experimental  argument  is  brought  forward  to 
show  that  the  elevation  of  the  temperature  of  the  body  in  fever 
creates  a.plrysical  medium  that  is  unfavorable  to  the  infectious 
organism. 

Nevertheless,  the  whole  school  of  which  I  have  already 
spoken  sees  in  pyretic  maladies  no  other  danger  than  that  which 
results  from  elevation  of  temperature.  Liebermeister  says  ex- 
pressly that  the  danger  in  fevers  lies,  above  all,  in  excessive 
elevation  of  temperature.  He  brings  forward  as  an  argument 
the  coagulation  and  decomposition,  at  44°  C.  (111.2°  F.),  of  the 
lecithine  which  enters  into  the  composition  of  the  nervous  ele- 
ments and  of  the  corpuscles  of  the  blood.  At  42°  C.  (107.6°  F.), 
at  43°  C.  (109.4°  F.),  and  even  at  41°  C.  (105.8°  F.),  the  nerve 
cells  show  abnormal  excitability  in  the  animal  experimented  upon. 


EFFECTS   OF   HIGH   TEMPERATURE.  203 

We  note  muscular  agitation,  acceleration  in  the  beating  of  the 
heart,  and  of  the  respiratory  movements.  The  phenomena  of 
osmosis  are  modified  by  thermic  elevation.  Water  is  retained  in 
the  cells.  The  tissues  of  those  suffering  from  fever  are  richer 
in  water  than  when  they  are  in  their  normal  state.  All  this  is, 
unfortunately,  true.  But  these  are  not  the  only  phenomena  to 
be  considered  in  cases  of  fever,  and,  moreover,  the  elevation  of 
temperature  in  illness  does  not  reach  44°  C.  (111.2°  F.),or  even 
43°  C.  (109.4°  F.),  unless  it  is,  exceptionally,  at  the  moment  of 
death  or  a  little  while  after  it. 

Naunyn  and  Rosenthal  have  studied  the  effects  of  excessive 
elevation  of  temperature  obtained  artificially.  At  44°  C.  (111.2° 
F.),  the  cardiac  muscle,  like  the  other  striated  muscles,  remains 
contracted,  and  death  ensues;  but  the  same  experimenters  were 
able  to  keep  rabbits  alive  for  weeks  ranging  between  41°  C. 
(105.8°  F.)  and  43°  C.  (109.4°  F.),  without  any  ill  effects  being 
observed. 

It  is  the  same  with  fatty  degeneration  of  the  viscera,  which 
I  studied  in  1867,  making  experiments  in  elevation  of  tempera- 
ture upon  a  dog.  I  caused  the  animal  to  raise  its  temperature 
itself,  simply  by  preventing  it  from  losing  the  greater  part  of  its 
heat.  It  lived  in  an  atmosphere  saturated  with  moisture,  and 
heated  to  a  degree  very  little  below  its  own  temperature.  Thus 
the  loss  of  caloric,  by  contact  and  by  evaporation,  was  sup- 
pressed ;  the  animal,  continuing  to  produce  caloric,  accumulated 
it.  The  effects  obtained  thus,  by  the  gradual  elevation  of  tem- 
perature, are  increased  action  of  the  heart  (300  beats)  and  of 
respiration  (80  to  90).  The  animal  died,  at  44°  C.  (111.2°  F.), 
at  the  end  of  about  four  hours.  Independently  of  hemorrhages 
under  the  pleura  and  the  pericardium,  we  observed,  four  hours 
after  the  commencement  of  the  elevation  of  temperature,  fatty 
degeneration  of  the  cardiac  muscle  and  of  the  hepatic  cells.  I 
was  led  to  think  that  the  excessive  elevation  of  temperature  was 
the  cause  of  the  fatty  degeneration,  but  Naunyn  and  Rosenthal 
found  that  no  similar  effect  was  prodiicc'd  in  animals  at  the 
excessive  temperatures  observed  in  man  when  suffering  from 
disease. 

On  the  other  hand,  elevation  of  temperature  does  not  seem 


204  LECTURES   ON   AUTO-INTOXICATION. 

to  increase  nutritive  metamorphoses  ;  the  waste  of  nitrogenous 
tissue  is  much  the  same  when  animals  are  subjected  to  elevation 
of  temperature  as  when  they  are  in  a  normal  condition.  (Sima- 
nowsky.)  Speaking  from  a  clinical  point  of  view,  there  is  in  a 
patient  no  parallel,  notwithstanding  the  assertions  of  Hirtz, 
between  the  excretions  of  urea  and  the  elevation  of  temperature. 
It  cannot  be  said  that  high  temperature  appreciably  increases 
disassimilation.  Charvot  had  already  been  struck,  when  he 
was  studying  the  elimination  of  urea  in  typhoid  fever,  at  the 
slight  elimination  that  took  place  during  the  hyperthermic 
period,  whereas  it  increased  during  the  abatement  of  the  disease, 
and  still  more  during  the  period  of  convalescence.  I  pursued 
this  question  further,  studying  the  variations  in  the  weight  of 
the  body  in  typhoid  cases.  In  these  cases  all  the  combustions 
supposed  to  be  necessaiy  for  the  production  of  excessive  eleva- 
tion of  temperature  are  compensated  for,  the  diminution  in 
weight  being  quite  insignificant,  whereas,  when  they  enter  upon 
convalescence,  the  diminution  in  weight  is  rapid,  and  attains  its 
maximum  after  apyrexia,  when  food  is  administered  to  the 
patients.  Excessive  elevation  of  temperature  is,  therefore,  not 
a  source  of  danger  from  the  point  of  view  of  anatomical  lesions 
or  from  the  point  of  view  of  denutrition.  We  may  say,  there- 
fore, that  it  indicates  the  gravity  of  the  disease,  but  d*oes  not 
cause  it.  Elevation  of  temperature  announces,  but  does  not 
constitute,  the  danger.  It  is  even  an  established  fact  that 
the  accelerated  action  of  the  heart  which  accompanies  eleva- 
tion of  temperature  cannot  produce  exhaustion  of  the  heart ; 
the  functional  incapability  through  excess  of  work  is  a  myth, 
for  the  mechanical  work  effected  b}'  the  heart  is  less  when  the 
contractions  are  so  rapid  (200  to  300  pulsations).  The  relaxa- 
tion of  the  capillaries  and  the  diminution  of  the  arterial  and 
venous  tension  relieve  the  heart,  and,  from  the  point  of  view  of 
fatigue,  the  lessening  of  the  resistance  is  not  counterbalanced 
by  the  multiplication  of  the  cardiac  contractions. 

However,  these  considerations  do  not  alter  the  fact  that 
methods  of  lowering  the  temperature  are  useful  in  certain  cases, 
or  that  when  we  have  succeeded  in  lowering  the  temperature  we 
note  an  improvement  in  the  symptoms  and  an  amelioration  in 


SOURCES   OF   ABNORMAL   HEAT.  205 

the  general  condition  of  the  patient.  Although  the  complica- 
tions experienced  by  a  patient  whose  temperature  is  40°  C.  (104° 
F.)  or  41°  C.  (105.8°  F.)  do  not  seem  to  result  from  the  elevation 
of  temperature,  nevertheless  drugs  or  modes  of  treatment  that 
lower  this  excessive  temperature  cause  some  of  these  compli- 
cations to  disappear.  This  is  seen  to  be  the  case,  at  least,  with 
typhoid  fever  and  certain  cases  of  scarlatina  or  cerebral  rheu- 
matism, for,  except  in  these  three  diseases,  it  is  not  certain  that 
antipyretic  treatment  is  really  useful.  How,  then,  shall  we  deal 
with  excessive  elevation  of  temperature?  By  acting  upon  the 
causes  which  produce  normal  heat  or  abnormal  heat  ?  We  cannot 
choose  indiscriminately  between  these  two  methods.  We  may 
reduce  the  sources  of  normal  temperature  by  bleeding,  by  ab- 
stractions of  serum,  or  by  the  administration  of  poisons  producing 
the  same  effect  (veratrine  and  tartrate  of  antimony).  These 
methods,  long  in  use,  are  now  almost  entirely  abandoned. 

But  what  are  the  sources  of  abnormal  heat  ?  We  do  not  know 
yet,  we  can  only  surmise.  They  must  be  very  different  accord- 
ing to  different  diseases.  Are  they  normal  processes  carried  to 
excess,  or  are  they  abnormal  processes  that  raise  the  tempera- 
ture to  fever  height  ?  It  has  been  suggested  that  there  are  mi- 
crobes which  burn  side  by  side  with  normal  organisms  and  raise 
the  temperature  in  the  body  as  in  test-tubes.  This  is  merely  a 
hypothesis,  supported  by  analogies,  but  not  by  experiment. 

Another  hypothesis  is  that  of  the  retention  of  heat.  It  has 
been  said  that  tissue  wastes  more  quickly  in  fevers.  This  is  true 
in  certain  diseases;  in  acute  atrophy  of  the  liver,  for  instance; 
but  it  is  not  true  in  typhoid  fever.  Chalvet,  twenty  years  ago, 
observed,  after  Traiibe,  that  in  a  fever  patient  the  heat  radiation 
is  less  than  in  a  healthy  person.  A  squaiv  decimetre  of  his 
skin  loses  a  smaller  number  of  calories  than  a  square  decimetre 
of  the  skin  of  a  person  in  normal  health.  It  is  possible  that  a 
diminution  in  the  abstraction  of  caloric  results  from  this. 

The  rapid  diminution  of  the  corpuscles  of  blood  in  pyretic 
diseases  has  been  brought  forward  as  showing  a  more  rapid  de- 
struction of  matter.  Bockmann  replies  that  the  moment  the 
temperature  becomes  normal  again,  the  corpuscles  suddenly 
reappear.  They  remain  suspended  in  some  part  of  the  body 


206  LECTURES   ON    AUTO-INTOXICATION. 

during  the  fever.  Bockraaun  and  Naunyn  admit  that  they 
•are  temporarily  withdrawn  from  the  general  circulation.  This 
would  account  for  the  great  increase  in  volume  of  the  spleen. 
Hu'ter  has  observed,  in  septic  and  pyaemic  disorders,  globular 
stagnations  in  certain  parts  of  the  capillary  blood-vessels  ;  this 
fact  may  be  mentioned  as  corroborating  the  theory  of  a  tempo- 
rary abstraction  of  some  of  the  corpuscles. 

Winternitz  has  quite  recently  revived  the  opinion  that  the 
retention  of  heat  is  the  cause  of  fever.  Marey  also  attributed 
fever  to  a  defective  distribution  of  caloric.  If,  therefore,  certain 
fevers  ma}^  be  caused  by  the  retention  of  caloric,  it  may  be 
suggested  that  the  radiation  of  the  latter  should  be  increased. 
Riess,  experimenting  upon  animals  suffering  from  infectious  dis- 
eases, lowers  their  temperatures  artificially  until  they  become 
normal ;  but  the  diseases  continue  and  death  ensues.  The  danger, 
therefore,  does  not  lie  wholly  in  the  excessive  elevation  of 
temperature. 

Nevertheless,  I  repeat  that  clinical  experience  shows  that  the 
antithermic  treatment  is  advantageous.  How  then  does  it  act  ? 
Let  us  endeavor,  as  far  as  possible,  to  know  what  we  are  doing 
when  we  employ  antithermic  agents  ;  those  that  have  been  used 
successfully  are  quinine,  salicylic  acid,  antipyrin,  kairin,  thallin, 
and,  above  all,  hydro-therapeutic  treatment. 

Murri  has  succeeded  in  showing  that  all  these  methods  raise 
the  temperature  of  the  skin,  and,  consequently,  bring  the  heat 
to  the  surface  of  the  body,  thus  favoring  the  lowering  of  the 
central  temperature.  Moreover,  they  do  not  act  upon  a  fever 
patient  in  the  same  way  as  upon  a  person  in  health.  Quinine 
does  not  lower  normal  temperature;  yet  it  can, in  typhoid  fever, 
cause  the  temperature  to  fall  three  degrees  in  a  few  hours.  In 
a  healthy  person  it  raises  it  one  or  two  tenths  of  a  degree,  but 
it  increases  the  flow  of  blood  to  the  skin.  This  is  true  in  a 
higher  degree  of  salicj^lic  acid,  which  favors  perspiration  ;  like 
the  cold-bath  treatment,  which  at  first  physically  abstracts  a  few 
degrees  of  heat,  but  afterward  favors  the  relaxation  of  the 
cutaneous  capillaries,  the  congestion  and  heating  of  the  skin ; 
then  the  cooling,  at  the  surface  of  the  body,  of  a  larger  quantity 
of  blood  from  the  central  organs. 


EFFECTS   OF   ANTITHERMIC   TREATMENT.  207 

Theoretically,  the  cold-buth  treatment  increases  combustion, 
and  should  therefore  increase  calorification ;  this  is  true  in  the 
case  of  a  healthy  man,  who  then  produces  more  heat  than 
under  normal  conditions.  But,  in  the  fever  patient,  this  treat- 
ment retards  calorification.  In  typhoid  fever,  according  to  Ssis- 
setzky,  the  patient  does  not  give  off  any  more  carbonic  acid  and 
does  not  excrete  any  more  urea  when  he  is  subjected  to  refriger- 
ation. Taking  into  account  the  uncertainties  of  theory,  we  are 
justified  in  concluding  that  the  causes  of  fever  are  various ; 
that  it  depends  sometimes  on  an  increase  of  the  normal  calorifi- 
cation, sometimes  on  the  life  of  the  infectious  organisms,  and 
sometimes  on  the  retention  of  the  normal  heat.  In  any  case  we 
may  safely  say  that  the  antithermic  method  is  not  without  its 
uses  in  typhoid  fever ;  that  in  this  disease  quinine  is  useful ;  that 
it  answers  to  certain  indications  and  realizes  certain  effects  ;  that 
it  is  the  same  with  cold  baths  ;  but  that  in  other  disorders — 
pneumonia,  pleurisy,  etc. — this  antithermic  treatment  does  net 
offer  the  same  advantages. 


LECTURE  XXIII. 

PATHOGENIC  THERAPEUTICS  OF  TYPHOID   FEVER — NEW  MODE  OF 
BATHING  IN  FEVERS;  DIETING  OF  FEVER  PATIENTS. 

Uncertainties  regarding  the  nature  of  fever.  Probable  multiplicity  of  the  patho- 
genic sources  of  fever.  Impossibility  of  counteracting  it  by  pathogenic 
therapeutics.  Antipyretic  modes  of  treatment  acquired  by  empiricism. 
Antithermic  drugs.  Inconvenience  of  phenic  acid  and  antipyrin.  Utility  of 
quinine.  My  method  of  administering  quinine  in  typhoid  fever. Hydro- 
therapeutic  modes  of  treatment:  lotions,  wrappings,  baths.  The  methods 
of  Brand,  Liebermeister,  Ziemssen,  Riess.  Their  advantages  and  disadvan- 
tages. My  method :  tepid  baths,  gradually  cooled,  but  remaining  tepid. 
Details  of  their  administration.  Their  advantages. The  dieting  of  pa- 
tients in  typhoid  fever  and  other  long  fevers. Didactic  summary  of  my 

treatment  of  typhoid  fever.    Statistical  results. 

BEFORE  entering  upon  the  practical  side  of  the  antipyretic 
method,  it  would  be  expected  that  we  should  discuss  the  doc- 
trines concerning  the  nature  of  fever.  But,  in  examining  pyre- 
tological  doctrines,  we  are  met  at  every  point  by  contradictions, 
and  I  see  that  I  am  reduced  to  the  confession,  so  humiliating  to  a 
professor  of  general  pathology,  that  I  do  not  know  what  fever  is. 

Galen  was  not  troubled  with  these  uncertainties.  To  him 
febris  was  color  prseter  naturam.  This  is  a  definite  and  concise 
assertion,  and  the  resume,  as  it  were,  of  a  description  of  the 
morbid  state.  But  now  science  demands  further  particulars, 
and  wishes  to  know  the  origin  of  this  morbid  condition,  and 
what  is  the  source  of  fever. 

It  is  not  certain  that  there  is  one  pathogenic  source  of  fever. 
I  think,  myself,  there  are  several  pyretogenetic  processes.  We 
may  raise  the  temperature  of  a  body  in  various  ways,  by  com- 
bustion, radiation,  friction,  condensation,  etc. ;  in  the  same  way 
the  temperature  of  the  bodies  of  animals  may  be  raised  abnor- 
mally under  very  varying  conditions. 

Fever  may  be  the  result  of  an  increased  combustion  or  an 
increased  dehydration,  or  it  may  be  produced  by  the  liberation 
of  the  heat  produced  by  the  life  of  infectious  germs,  or  by  a 
diminution  in  the  losses  of  the  body,  or  by  resolution  of  the 
forces  of  tension. 
(208) 


THEORY   OF   FEVER.  209 

In  the  living  organism  forces  exist  that  are  developed  by  the 
metamorphosis  of  the  matter  in  the  cells,  and  which  do  not  act 
externally,  either  by  motion  or  by  heat.  Life  is  a  sort  of  un- 
stable equilibrium  that  is  maintained  by  the  forces  of  tension. 
These  oppose  the  freedom  of  the  chemical  and  physical  actions, 
where  opposite  electrical  actions  meet,  the  acids  and  alkalies. 
J.  Ranke  proved,  long  ago,  that  the  nucleus  of  a  living  cell 
is  electro-positive,  whereas  its  envelope  is  electro-negative. 
Why  do  not  these  opposing  kinds  of  electricity  combine  to 
bring  about  a  condition  of  electrical  neutrality,  unless  it  is 
because  they  are  prevented  by  the  opposing  forces  of  tension  ? 
If  death  occur,  neutralization  is  immediate. 

It  is  the  same  with  the  nerves  as  regards  the  electrical  con- 
dition of  the  axis-cylinder  and  of  the  envelope ;  the  former  is  acid, 
the  latter  alkaline,  during  life  ;  upon  death,  neutralization  ensues. 
The  combustion  being  the  same,  if  the  tension  is  diminished, 
part  of  the  force  will  become  apparent  under  the  form  of  heat. 
Is  this  theory  regarding  fever  applicable  to  certain  forms  of 
pyrexia  ?  I  do  not  know.  We  can  only  form  h}rpotheses  on 
this  subject.  Remember  what  I  said  about  uraemia.  We  have 
found  poisons,  but  not  the  poison  of  unemia.  As  regards  fever, 
there  may  exist  not  one  single  explanation,  but  various  patho- 
genic conditions.  I  have,  moreover,  called  attention  only  to 
those  processes  for  which  experimental  or  clinical  data  can  be 
furnished. 

In  short,  fever  is  with  us  as  with  Galen, — elevation  of  tem- 
perature arising  from  causes  that  may  strangely  vary.  Now, 
from  a  therapeutic  point  of  view,  not  being  sure  what  fever  is, 
we  are  compelled  to  give  up  the  idea  of  drawing  up  a  system  of 
pathogenic  therapeutics  for  its  treatment. 

We  are  thus  obliged  to  return  to  empiricism,  which  is  not 
sufficient  to  satisfy  us,  but  which  can  give  us  information  result- 
ing from  the  long  accumulation  of  individual  facts.  Let  us, 
therefore,  enter  the  domain  of  empirical  observations. 

We  know,  empirically,  that  certain  modes  of  treatment  lower 
the  temperature  and  bring  about  an  improved  state  of  affairs. 
Thus,  in  the  first  place,  quinine  has  evidently  a  beneficial  action 
on  typhoid  fever  and  some  other  forms  of  pj'rexia,  intermittent 


210  LECTURES   ON    AUTO-INTOXICATION. 

fever,  and  in  one  form  of  infection  of  women  in  childbed ;  its 
action  is  undoubtedly  favorable,  but  it  is  only  temporary. 

Phenic  acid  has  a  certain  antipyretic  action,  but  perhaps  not 
a  favorable  one  ;  autipyrin  has  also  this  action,  but  its  influence 
is  unfavorable.  When  the  temperature  is  at  40°  *  or  41°  C.,  a  suf- 
ficient dose  of  quinine  produces  a  fall  of  from  1  to  3  degrees,  which 
may  last  for  twenty-four  hours.  At  the  same  time,  we  note  also 
the  disappearance  or  diminution  of  the  nervous  troubles  that 
were  attendant  upon  the  high  temperature ;  the  patient  is  evi- 
dently better,  and  accidents  which  might  soon  cause  death  may 
thus  be  averted.  It  would,  therefore,  on  first  thoughts,  seem 
advisable  to  prolong  indefinitely  this  favorable  effect.  Vogt 
twenty  years  ago,  and  Joft'roy  recently  at  the  Hotel-Dieu,  have 
tried  the  continuous  administration  of  quinine.  I  also  wished  to 
see  what  results  could  be  obtained  by  this  means.  I  was  soon 
obliged  to  abandon  the  experiment.  With  2  grammes  of  quinine 
we  get  a  fall  of  1,  2,  or  3  degrees  ;  but  in  the  evening  of  the  next 
day  the  temperature  rises  again,  and  by  the  morning  of  the  fol- 
lowing day  the  fever  has  reached  its  original  height.  Should 
quinine,  therefore,  be  administered  in  the  evening  as  a  prevent- 
ive ?  But  the  second  dose  does  not  produce  the  same  effects. 
Three  days  at  least  must  elapse  before  the  quinine  regains  its 
power.  It  is  an  intermittent  remedy.  It  has  been  asserted  that 
if  given  continuously  the  temperature  varies  between  39°  and 
40°  C.,  instead  of  between  40°  and  41°  C.  Is  this  advantage  suf- 
ficient? As  for  myself,  I  never  give  a  second  dose  of  quinine 
until  after  an  interval  of  sevent3'-two  hours.  I  only  give  it  then 
if  the  temperature  taken  in  the  morning  in  the  rectum  exceeds 
40°  C.,  or  if  that  taken  in  the  evening  exceeds  41°  C.  The 
doses  that  I  have  adopted  are  2  grammes  during  the  first  and 
second  periods  of  seven  days ;  1^  grammes  in  the  third  period ; 
1  gramme  in  the  fourth  and  after.  I  never  give  less  than  this  ; 
^  gramme  would  be  of  no  use.  It  is  well  to  know  that  from 
the  eighth  to  the  eleventh  day  we  often  obtain  only  a  slight 
lowering  with  doses  that  are  generally  efficacious  either  before 
that  time  or  after.  This  is  almost  necessarily  the  effect  produced 

*  40°  C.  equal  104°  F.  To  convert  degrees  Centigrade  into  Fahrenheit  multiply 
by  9,  divide  by  5,  and  add  32  to  the  result. 


SUDDEN   DEATH   IN   FEVER   ATTRIBUTED   TO   QUININE.  211 

by  quinine;  it  aims  only  at  an  accident, viz.,  the  excessive  ele- 
vation of  temperature. 

As  for  other  remedies  that  are  reputed  to  be  antithermic, — 
phenic  acid,  resorcin,  antipyrin,  thallin, — you  cannot  depend  upon 
them.  In  regard  to  antipyrin,  the  lowering  that  it  produces  is 
rarely  accompanied  by  an  improved  general  condition,  for  it 
causes  at  the  same  time  a  lowering  of  nervous  activity.  The  only 
objection  to  quinine,  setting  aside  the  buzzing  in  the  ears,  which, 
however,  affects  fever  patients  less  than  persons  in  health,  is  the 
accusation  urged  against  it  that  it  is  liable  to  cause  sudden  death. 
During  ten  years,  out  of  five  hundred  cases,  I  have  only  found 
sudden  death  occur  seven  times  with  patients  who  were  taking 
quinine.  Four  of  these  deaths  happened  in  the  same  week  ;  and 
in  several  hospitals,  at  the  same  time,  similar  cases  came  under  my 
notice.  But  chemical  analysis  showed  that  the  drug  administered 
to  the  patient  under  the  name  of  quinine  was  really  not  quinine. 
It  was  a  compound  little  known,  in  which  cinchonine  predomi- 
nated. If  we  set  aside  these  cases,  therefore,  there  remains  three 
cases  of  sudden  death  out  of  five  hundred  cases  of  typhoid  fever, 
— a  proportion  which  does  not  exceed  the  ordinary  percentage 
of  sudden  death  in  this  malady.  The  post-mortem  examination 
showed  that  in  the  patients  that  had  died  suddenly  the  heart 
was  contracted  and  absolutely  empty  of  blood.  Now,  the  toxi- 
cology of  quinine  teaches  us  that  when  death  is  caused  by  this 
drug  the  heart  is  found  to  be  dilated  and  gorged  with  blood. 
Moreover,  since  that  time,  I  have  not  had  a  case  of  sudden  death. 

In  short,  then,  I  consider  that  by  administering  quinine  to 
typhoid  patients, according  to  the  rules  already  stated,  we  obtain, 
as  well  as  a  diminution  of  temperature,  an  improved  condition 
generally.  But  I  must  add  that  in  most  other  forms  of  pyicxia 
this  treatment  has  failed.  In  pneumonia,  pleurisy, and  erysipelas, 
we  obtain,  as  a  rule,  neither  a  full  of  temperature  nor  an  im- 
proved general  condition. 

Abstraction  of  heat  is  the  only  non-medicinal  means  of 
lowering  the  temperature  of  fever  patients.  Many  methods  of 
abstracting  heat  in  fever  patients  have  been  tried.  Since  the 
time  of  Sydenham  and  Currie,  cold  air  has  been  used,  currents 
of  air  between  open  windows,  and  cold  water  in  various  ways. 


212  LECTURES   ON   AUTO-INTOXICATION. 

The  continuous  sprinkling  of  the  patient  is,  perhaps,  the 
most  painful  process.  A  cold  shower-bath  also  produces  a  dis- 
agreeable nervous  action.  Bathing  with  cold  water  gives  an 
unpleasant  shock,  and  the  abstraction  of  heat  by  these  two 
methods  is  very  slight.  Wrapping  in  a  wet  sheet  is  painful  for 
some  moments. 

Local  applications,  such  as  a  bladder  of  ice  on  the  abdomen, 
produce,  at  first,  a  vascular  spasm,  and  then  stasis  in  the  vessels  ; 
the  skin  is  chilled  and  the  cellular  tissue  also ;  necrosis  may  set 
in,  but  the  body,  as  a  whole,  is  not  cooled. 

The  circulation  of  cold  water  by  means  of  the  ingenious  con- 
trivances of  Dumontpallier  and  Clement  produce  a  real  refriger- 
ation, but  these  processes  are  little  used  as  yet,  and  I  am  not, 
therefore,  in  a  position  to  express  an  opinion  as  to  their  merit. 

Enemata  of  cold  or  iced  water  certainly  cool  the  rectum, 
but  they  do  not  produce  a  general  reduction  of  temperature. 

It  now  remains  for  us  to  speak  of  the  method  which  is  gen- 
erally preferred, — the  ordinary  bath,  in  which  the  temperature 
of  the  water  is  lower  than  that  of  the  body  of  the  patient. 

The  cold  bath  may  be  given  according  to  the  method  of  Brand 
or  Liebermeister.  According  to  Brand,  when  the  temperature 
exceeds  38.5°  C.,  a  bath  of  low  temperature  is  given  eight 
times  a  day,  for  from  ten  to  fifteen  minutes. 

Liebermeister  leaves  the  patient  in  the  bath  throughout  the 
whole  course  of  the  illness ;  the  duration  is  the  same,  and  he 
gives  twelve  baths  a  day.  The  temperature  may  be  15°  C., 
but  this  has  been  abandoned ;  from  18°  to  20°  C.  is  the  general 
rule ;  it  may  be  even  25°  C.  Care  must  be  taken  to  apply  cold 
water  to  the  head  first. 

The  patient  is  left  in  the  bath  until  the  cold  chill  is  complete, 
and  he  is  often  taken  out  in  an  alarming  state.  Our  feelings 
must  be  well  under  control  if  we  are  to  carry  out  this  treatment 
rigorously  in  face  of  the  sufferings  of  the  patients.  It  is  worth 
mentioning  that  if  we  cause  them  great  suffering  we  can  almost 
guarantee  their  recovery.  But  is  there  no  treatment  that  is  as 
efficacious  without  being  so  inhuman  ? 

The  cruelty  of  cold  baths  has  led  to  tepid  baths  being  sub- 
stituted for  them.  There  is  the  tepid  bath  at  a  disagreeably  low 


FEVER-TREATMENT    BY   BATHS.  213 

temperature,  viz.,  28°  C.,  which  might  as  well  be  called  a  cold 
bath ;  for  to  a  man  whose  temperature  is  40°  C.  the  sensation  is 
the  same  at  28°  C.  as  at  25°  or  20°  C. 

Ziemssen  has  proposed  a  tepid  bath,  gradually  cooled.  The 
temperature,  at  first,  is  35°  C.,  and  to  a  fever  patient  even  this 
gives  a  very  unpleasant  sensation  of  cold.  Then  the  tempera- 
ture of  the  bath  is  rapidly  lowered,  so  that  in  ten  minutes  it 
fulls  to  25°  C.  The  patient  remains  in  this  cold  bath  for  from 
ten  to  fifteen  minutes,  until  the  teeth  begin  to  chatter,  as  in  the 
methods  of  Brand  and  Liebermeister.  This  is  the  cold  bath 
preceded  by  a  short  phase  of  bearable  temperature.  But  this 
method  does  not  do  away  with  the  sudden  nervous  shock. 

I  will  also  mention  Riess's  continuous  bath,  which  lasts 
twenty-four  hours  a  day  at  a  temperature  of  34°  C.  The  tem- 
perature is  moderated  b}-  this  method,  which  may  be  useful. 
The  mortality  would  be  6  per  cent.,  according  to  Riess,  but 
his  statistics  are  only  derived  from  forty-eight  cases.  This 
continuous  tepid  bath  becomes  rapidly  unbearable,  and  the 
patients  prefer  the  cold  baths  according  to  Brand's  method. 

I  will  now  describe  my  own  method,  which  I  have  been  trying 
for  more  than  a  year.  My  object  was  to  develop  a  bath  in  which 
the  patient  might  lose  heat  without  anj'  nervous  shock  or  spasm 
of  the  cutaneous  vessels.  What  we  wish  to  arrive  at  is  not 
merely  abstraction  of  heat  by  contiguity  or  conductivity.  On 
the  contrary,  what  we  require  is  that  the  blood  should  come  from 
the  centre  of  the  body  to  the  surface  to  be  cooled. 

The  temperature  of  the  bath,  at  first,  is  two  degrees  below  the 
central  temperature, — 38°  C.,  for  instance,  if  the  temperature  of 
the  patient  is  40°  C.  The  patient  can  bear  this  well  and  experi- 
ences no  shock.  The  water  is  gradually  cooled  at  the  rate  of 
one-tenth  degree  per  minute,  or  one  degree  in  ten  minutes,  until 
it  is  lowered  to  30°  C.,  but  it  is  never  cooled  beyond  this  point. 
The  time  necessary  for  this  cooling  is  an  hour  and  a  half  if  the 
temperature  of  the  patient  is  40°  C.,or  an  hour  and  ten  minute-; 
if  it  is  38°  C. 

No  feeling  of  nervous  shock  and  no  peripheral  vascular  spasm 
occur  during  this  long  period.  The  pulse  is  not  constricted. 
At  about  33°  C.  the  patient  finds  his  bath  cool ;  at  32°  C.  he  finds 


214  LECTURES   Otf   AUTO-INTOXICATION. 

it  cold,  but  even  at  30°  C.  he  continues  to  speak  and  talk,  show- 
ing a  wonderful  mental  condition.  He  has  nothing  of  the  typhus 
stupor  about  him.  The  lowering  of  temperature  realized  is  much 
more  considerable  than  with  the  cold  bath. 

I  give  the  bath  eight  times  a  day,  like  Brand.  Certain  pa- 
tients can  thus  pass  half  the  day  in  the  water.  The  lowering  of 
the  temperature  is  more  lasting  than  with  the  cold  bath,  and 
sudden  rises  of  temperature  are  much  less  considerable. 

By  plunging  a  patient  into  a  bath  which  is  only  two  degrees 
below  his  own  temperature,  I  do  not  provoke  the  reflex  vascular 
spasm  that  prevents  the  blood  from  coming  to  the  skin  to  be 
cooled.  The  lowering  of  the  temperature  of  the  water  is  effected 
insensibly,  and  never  transforms  the  bath  into  a  cold  one. 

*  What  are  the  effects  that  result  from  baths  administered  ac- 
cording to  the  mode  that  I  recommend  ?  An  almost  constant 
lowering  of  the  central  temperature,  a  refrigeration  which  varies 
according  to  the  stage  of  the  disease  and  the  hour  of  the  day. 
The -cooling  is,  on  an  average,  five-tenths  of  a  degree;  it  may 
sometimes  amount  to  three  degrees.  I  speak  from  an  experience 
supported  by  the  results  of  six  thousand  baths.  Some  excep- 
tions should  be  mentioned.  For  instance,  in  certain  patients  the 
temperature  is  not  reduced  ;  we  even  observe  a  rise  of  tempera- 
ture of  one-  to  five- tenths  of  a  degree.  This  anomaly  is  seen  in 
certain  very  nervous  women,  and  in  certain  men  toward  the  end 
of  the  treatment,  when  the  repetition  of  the  baths  has  ended  by 
developing  in  them  an  insurmountable  repugnance  and  keen  irri- 
tation. 

The  elevation  of  temperature  which  takes  place  after  the  bath 
is  slow;  it  is  never  a  sudden  rise. 

It  is  to  be  remarked  that  we  succeed  better  in  cooling  the 
patient  in  proportion  as  his  temperature  is  higher,  so  long  as 
his  temperature  remains  between  37°  and  40°  C. ;  but,  on  the 
contrary,  with  patients  whose  temperature  is  excessive,  above 
40°  and  41°  C.,  the  cooling  is  slighter  in  proportion  as  the  tem- 
perature is  higher.  The  lowering  is  less  between  41°  and  42°  C. 
than  between  40°  and  41°  C.  Below  38°  C.,  also,  cooling  is  diffi- 
cult ;  a  man  in  health  is  scarcely  cooled  at  all  in  a  tepid  bath. 

The  differences  in  the  lowering  of  the  temperature  in  the  baths 


EFFECTS   OF  BATHS.  215 

vary  also  according  to  the  periods  of  the  disease.  In  that  stage 
where  excessive  temperature  is  the  leading  feature,  and  at  the 
commencement,  it  is  more  difficult  to  cool  the  patients  ;  the  aver- 
age fall  is  five-tenths ;  later  on  it  is  six-tenths ;  and  in  the  fourth 
week,  seven-tenths. 

There  are  also  variations  according  to  the  time  of  day.  The 
temperature  of  a  typhoid  patient  rises  from  7  o'clock  in  the 
morning  to  3  o'clock  in  the  afternoon ;  then  a  diminution 
takes  place,  and  after  that  another  rise,  the  maximum  of  which 
is  reached  about  midnight.  From  midnight  to  7  o'clock  it 
abates  again,  and  the  patient  loses  the  excess  of  temperature 
that  he  had  gained  during  the  day.  It  is  between  midnight  and 
6  o'clock  in  the  morning  that  the  most  important  diminutions 
of  temperature  are  obtained  after  the  bath  ;  a  fall  of  three  degrees 
is  often  observed  toward  morning. 

Do  the  patients  derive  any  other  benefits  from  the  baths  be- 
sides the  physical  abstraction  of  heat  ?  Without  doubt  they  do. 
In  the  first  place  the  lowering  of  temperature  resulting  from  the 
bath  is  accompanied  by  an  improved  general  condition,  as  with 
quinine ;  whereas  with  the  diminution  of  heat  obtained  by  means 
of  antip3-rin  the  general  condition  remains  the  same  or  grows 
worse. 

Other  advantages  also  are  obtained.  When  delirium  sets  in 
at  the  commencement,  it  abates  after,  at  the  most,  three  days  of 
the  treatment.  There  is  no  more  of  the  real  typhus  stupor.  The 
patients  that  are  treated  by  the  baths  do  not  cease  to  understand 
what  is  said  to  them  and  to  answer  questions. 

According  to  Skinner,  one  of  my  pupils  who  has  written  a 
very  good  thesis  on  the  study  of  my  system  of  baths,  we  find 
that  the  patients  always  take  great  interest  in  the  variations  of 
their  temperature,  and  discuss  among  themselves  during  the  bath 
the  number  of  tenths  of  a  degree  noted  before  and  after. 

The  tongue  remains  moist,  and  if  dry  at  the  beginning  of  the 
treatment,  this  dryness  disappears  after  a  few  baths.  The  teeth 
are  not  discolored.  The  complexion  has  not  tlint  e:irtliy  pallor 
that  denotes  the  thorough  poisoning  of  the  system.  It  is  wliito 
and  often  even  pink  in  those  patients  that  have  a  fine  skin. 

Lastly,  the  need  of  sleep  manifests  itself  M  l't«  r  r.-u-h  lmtli,and 


216  LECTURES  ON   AUTO-INTOXICATION. 

the  patients  enjoy  sleep  at  night, — an  unusual  thing  with  typhoid 
patients.  For  this  last  reason  I  do  not  give  baths  from  2  to  6 
o'clock  in  the  morning,  for  fear  of  disturbing  this  night-sleep, 
which  is  precious.  Only  in  order  to  give  the  eight  baths  in  the 
twent3r-four  hours,  the  intervals  between  them  should  be  a  little 
shorter  from  3  o'clock  to  midnight.  Amongst  the  advantages  of 
the  baths  I  may  mention  the  rarity  of  eschars. 

But  all  these  results  are  obtained  from  tepid  baths  in  typhoid 
fever  only.  We  have  said  that  cold  baths  could  be  employed  in 
pneumonia,  erysipelas,  and  pleurisy.  I  tried  in  these  diseases 
cold  baths  and  tepid  baths  systematically  cooled.  I  did  not  in 
these  cases  observe  the  salutary  effects  which  are  so  evident  in 
typhoid  fever. 

Thus  I  do  not  think  that  this  can  be  called  a  general  anti- 
thermic method.  Perhaps,  however,  it  would  be  applicable  to 
certain  hyperthermic  forms  of  scarlatina  and  cerebral  rheuma- 
tism. I  cannot  speak  from  personal  experience  on  this  point. 
I  have,  however,  observed  remarkable  results  from  it  in  measles. 

Are  there  no  disadvantages  attendant  upon  this  system  of 
tepid  baths  gradually  cooled  ? 

We  cannot  attribute  to  them  pulmonary  congestion,  which  is 
neither  more  frequent  nor  more  marked  than  with  other  modes 
of  treatment,  and  which,  on  the  contrary,  veiy  often  decreases 
during  the  baths.  Neither  pneumonia,  pleurisy,  nor  any  other 
grave  visceral  lesion  has  been  reported  as  resulting  from  the 
baths.  But  when  the  epidermis  at  last  becomes  puffy  and 
macerated  at  the  palms  of  the  hands  and  the  soles  of  the  feet, 
we  often  find,  in  the  case  of  workmen,  or  in  cases  where  the 
epidermis  is  very  thick,  that  whitlows  and  accumulations  of  pns 
close  to  the  nails  form  under  the  skin.  Besides  this  inflam- 
matory complication,  it  is  not  unusual  to  find,  after  a  few  baths, 
a  rather  painful  glandular  swelling  in  the  axilla,  but  never  real 
adenitis.  The  hands  and  feet  must  be  watched  so  as  to  let  out 
the  pus  as  soon  as  it  is  observed,  or  we  shall  find  that  extensive 
inflammation  of  the  lymphatics  will  soon  ensue.  However,  these 
are  accidents  of  minor  importance. 

I  discontinue  the  use  of  the  baths  in  the  event  of  intestinal 
hasmorrhage  or  pulmonary  hepatization.  When,  in  a  female 


OBJECTIONS   TO   MILK.  217 

patient,  the  menstrual  period  occurs  during  the  course  of  typhoid 
fever,  I  do  not  generally  find  it  necessarj'  to  interrupt  the  baths. 

I  now  come  to  an  important  point  in  the  therapeutics  of 
grave  pyretic  diseases, — the  question  of  diet. 

In  these  disorders,  and  especially  in  typhoid  fever,  the  secre- 
tions of  the  digestive  tube  are  dried  up  or  perverted.  It  seems, 
therefore,  a  priori  impossible  to  feed  the  patients,  and  natural 
to  condemn  all  attempts  at  alimentation. 

Milk,  which  is  so  easy  to  digest,  and  which  from  its  fatty 
nature  and  its  sugar  seems  so  well  adapted  to  keep  up  the  strength 
of  fever  patients,  and  make  up  for  the  waste  by  combustion,  is 
not  without  its  drawbacks.  It  raises  the  temperature,  and  the 
urinary  secretion  is  lessened.  Those  who  are  in  favor  of  a  milk 
regimen  order  a  large  quantity  to  be  given  in  typhoid  fever  so 
as  to  increase  the  urinarj^  secretion.  Now,  when  I  give  milk 
in  any  considerable  quantity,  I  notice  that  it  causes,  through 
indigestion,  an  aggravation  of  the  patient's  condition.  I  there- 
fore maintain  that  all  food  should  be  rigorouslj-  withheld.  But 
I  give  water  in  abundance,  and  water  containing  substances  that 
are  slightly  nutritive  and  capable  of  introducing  into  the  system 
certain  mineral  elements,  under  the  form  of  meat  extract,  broth, 
and  cereal  extract.  This  latter  was  considered  useful  in  fever 
cases  two  thousand  years  ago.  The  ptisan  of  Hippocrates  was  a 
decoction  of  bade}';  strained  ptisan  was  prescribed  at  the  begin- 
ning of  fevers,  and  ptisan  that  was  not  strained  at  the  end.  I 
give  my  patients  an  extract  of  meat  and  barley  which  contains 
mineral  elements  that  are  calculated  to  repair  the  losses  resulting 
from  the  disassimilation  of  mineral  material  in  the  cells.  I  en- 
deavor to  prevent  the  waste  of  mineral  matter,  as  it  plnys  tlu> 
part  of  middle-man  in  organic  changes.  Chloride  of  sodium  is 
indispensable  for  the  phenomena  of  osmosis  ;  phosphates  are  the 
mediums  between  the  bases  and  the  acids. 

To  this  regimen  I  add  vegetable  acids,  in  the  form  of  lemon- 
juice,  which  introduces  potass,  and  which  is  combustible. 

Lastly,  I  administer  substances  that  nre  both  plastic  and 
combustible, — peptones.  I  give  50  grammes  *  per  day,  ivi-kiming 
the  dry  peptone.  These  peptones,  which  are  chemicall}'  pure 

» I.e.,  a  little  more  than  1%  ounces  of  dry  peptone. 


218  LECTURES   ON    AUTO-INTOXICATtOtf. 

and  prepared  honestly,  and  are  very  different  from  certain  prod- 
ucts sold  under  the  same  name  in  commerce,  are,  as  we  have 
said,  plastic  combustible  substances  calculated  to  make  up  for 
the  waste  of  nitrogenous  matter  in  the  body. 

In  the  regimen  of  our  typhoid  patient  another  substance  that 
figures  as  a  combustible  agent  is  fat  in  a  form  that  can  be  ab- 
sorbed, i.e.,  glycerin  formed  outside  of  the  system  ;  for  we  know 
that  glycerin  is  one  of  the  products  of  the  division  of  fatty  sub- 
stances in  the  duodenum.  The  patient  absorbs  every  day  200 
grammes  of  glycerin,  and  }'et  is  not  purged.  I  only  allow  wine 
in  very  small  quantities. 

This  is  the  whole  of  my  system  of  dietetics.  Thanks  to  it, 
only  a  very  slight  loss  of  weight  is  observed  during  the  period 
of  fever.  The  loss  of  weight  is  sometimes  nil;  it  varies  gen- 
erally between  100  and  300  grammes  a  day  up  to  the  end  of  this 
period,  as  far  as  the  fifteenth  day ;  later  on,  at  the  moment  of 
the  crisis,  and  when  convalescence  is  established,  the  loss  may 
amount  to  1  kilogramme  per  day  for  three  to  five  days  ;  but, 
from  the  third  day  after  alimentation  is  resumed,  the  weight  of 
the  patient  increases  again.  Several  principles  of  this  dietary 
are  applicable  to  the  intense  fever  of  certain  chronic  maladies. 
In  the  acute  p}rrexia  of  very  short  duration,  as  in  pneumonia, 
the  necessity  for  alimentation  is  not  so  urgent. 

I  will  now  sum  up  briefly  and  didactically  the  rules  for  the 
treatment  of  typhoid  fever  as  I  have  just  described  it.  These 
rules  may  be  classed  under  four  main  headings  :  the  general 
antiseptic  treatment,  the  intestinal  antiseptic  treatment,  the 
antithermic  treatment,  and  the  regimen  to  be  observed. 

As  soon  as  the  diagnosis  is  made  or  suspected,  I  prescribe: 

(a)  A  purgative,  to  be  repeated  regularly  every  three  days 
(15  grammes  of  sulphate  of  magnesia). 

(6)  Forty  centigrammes*  of  calomel  per  day,  in  20  doses  of 
2  centigrammes  (one  every  hour),  are  administered  for  four  con- 
secutive days.  This  constitutes  the  general  antiseptic  treatment. 

(c)  The  intestinal  antiseptic  treatment  consists  in  mixing 
100  grammes  of  powdered  vegetable  charcoal  with  1  gramme  of 
iodoform  and  5  grammes  of  naphthalin.  The  whole  is  mixed 

*  40  centigrammes  equal  6.2  grains. 


SYSTEMATIC  TREATMENT  OF  FEVEB.  21 9 

with  200  grammes  of  glycerin  and  with  the  50  grammes  of  pep- 
tone that  form  the  basis  of  nourishment.  This  mixture  forms 
a  black,  semi-liquid  paste,  which  is  taken  in  twenty-four  hours 
in  doses  of  a  tablespoon ful  every  two  hours  in  a  third  of  a  glass 
of  water.  I  wash  out  the  bowels  regularly  ever}'  morning  and 
evening  by  means  of  an  injection  containing  1  part  in  1000  of 
phenic  acid,  each  injection  consisting  of  50  centigrammes  of 
phenic  acid  to  500  grammes  of  water. 

(d)  Fjrom  the  first  day  the  patient  takes  eight  baths  a  day 
until  he  is  completely  cured,  when  the  temperature  varies  between 
37°  and  38°  C.    The  baths  are  resumed  if  the  temperature  exceed 
37.5°  C.     I  reserve  quinine  for  cases  in  which,  notwithstanding 
the  baths,  the  temperature  remains  too  high.      The  doses  are 
2  grammes  during  the  first  two  periods  of  seven  days,  l£  grammes 
during  the  third  period,  and  1  gramme  during  the  fourth  and  fifth. 
These    quantities   are  administered   in    large   doses — 50   centi- 
grammes— every  half-hour.    But  I  do  not  return  to  quinine  until 
after  an  interval  of  three  days.     The  signal  for  the  employment 
of  quinine  is  a  temperature  in  the  rectum  of  40°  C.  in  the  morn- 
ing or  41°  C.  in  the  evening.    Often  the  baths  dispense  with  the 
nse  of  quinine  and  constitute  in  themselves  a  sufficient  system 
of  antithermic  treatment. 

(e)  The  diet  comprises :   broth  cooked  with  barley  and  ad- 
ministered  freely  (l£  litres  to  2  litres  a  day)  ;   glycerin  (asso- 
ciated, as  I  have  said,  with  charcoal,  iodoform,  and  naphtlialin, 
and  also  with  peptones)  ;  lemonade  made  from  lemons,  with  the 
addition  of  a  little  wine.     This  is  certainly  a  complicated  sj-stem 
of  therapeutics ;  it  cannot  be  otherwise,  as  the  indications  to  be 
fulfilled  are  complex. 

This  systematic  treatment,  te  it  understood,  does  not  exclude 
the  treatment  of  certain  accidents ;  for  instance,  excessive  or 
prolonged  delirium  by  opium,  pcritonitic  complications  l>y  nic:ms 
of  ice  or  Neapolitan  ointment.  I  have  only  discussed  those 
symptoms  that  are  common  to  all  patients;  for  if,  as  has  been 
said,  we  are  to  study  the  patients  and  not  the  disease,  it  is  no 
less  true  that  all  patients  show  in  their  illnesses  general  featmv* 
without  which  they  would  not  have  the  disease  at  nil.  Why 
should  I  be  reproached  for  employing  a  systematic  mode  of 


220  LECTURES   ON    AUTO-INTOXICATION. 

treatment?  Is  it  not  as  natural  to  contend  systematically  with 
excessive  temperature,  infection,  and  self-poisoning,  as  it  is  to 
feed  one's  self  systematically  every  day  ?  When  I  discontinued 
the  baths  for  some  reason  in  the  course  of  the  illness,  the  tem- 
perature in  the  patients  went  up  again  to  40°  and  41°  C.,  and 
sometimes  they  died. 

What  results  have  I  obtained  from  my  method  ? 

Formerly  the  mortality  from  typhoid  fever,  in  the  cases  that 
came  under  my  notice,  was  25  per  cent.  When  I  succeeded  in 
neutralizing  the  intestinal  poisons,  it  fell  to  15  per  cent.,  then  to 
10  per  cent.,  when  I  obtained  a  successful  intestinal  antiseptic 
treatment.  It  has  fallen  to  7  per  cent,  since  I  instituted  the 
complete  system  of  treatment,  which  was  in  April,  1884. 

This  is  a  better  result  than  Liebermeister  has  obtained  by 
cold  baths.  And  I  reckon  the  total  mortality,  including  patients 
that  arrive  at  the  hospital  at  a  very  advanced  stage  of  the  fever, 
without  having  been  treated  at  all,  having,  as  I  found  in  one 
case,  a  temperature  of  42.6°  C.,  and  those  who  are  brought  to 
us  already  attacked  with  peritonitis  through  perforation  ;  I  in- 
clude deaths  that  may  be  attributed  to  later  complications,  cases 
in  which  the  treatment  has  been  suddenly  discontinued  for  some 
cause  or  other,  and  those  cases  in  which  the  method  has  not 
been  strictly  carried  out.  Thus,  in  the  beginning,  when  it  was 
not  possible  for  me  to  arrange  for  baths  at  night,  in  the  case  of 
one  patient,  the  temperature,  which  had  fallen  during  the  day 
under  the  influence  of  the  baths,  rose  in  the  night  to  42°  C., 
and  the  third  night  he  died. 

The  number  of  patients  that  have  been  subjected  to  the  com- 
plete treatment  is  now  one  hundred  and  twent}r-nine,*  out  of 
which  there  have  been  nine  deaths,  showing  a  mortality  of  7 

*At  the  date  of  this  publication  (November,  1886)  the  number  of  cases  of 
typhoid  fever  treated  by  M.  Bouchard's  staff  at  the  Lariboisiere  Hospital  since 
April  1,  1884,  is  two  hundred  and  twenty-six,  out  of  which  there  have  been  thirty-one 
deaths,  or  a  mortality  of  11.7  per  cent.  Is  this  increased  rate  of  mortality  to  be  at- 
tributed to  a  chance  accumulation  of  critical  cases,  or  to  a  modification  introduced 
into  the  treatment,  salicylate  of  bismuth  having  been  substituted  for  the  charcoal,  and 
the  peptones  having  been  suppressed  against  his  will,  during  a  considerable  period  ? 
But  in  any  case  11.7  per  cent,  is  low  as  compared  with  the  general  mortality  in  this 
hospital.  The  Lariboisiere  Hospital  has  been  open  a  third  of  a  century,  and  during 
that  time  the  average  mortality  in  typhoid  fever  has  been  21  per  cent.  It  is  still  18 
per  cent,  for  the  last  six  years. 


IMPROVED  MORTALITY   STATISTICS.  221 

per  cent.  The  mean  duration  of  the  illness  has  been  nineteen 
days.  The  frequent  relapses  which  attack  20  per  cent,  of  the 
patients  have  fallen  to  10  per  cent,  in  the  last  period.  In  fact, 
we  have  every  reason  to  congratulate  ourselves  on  these  results ; 
and  I  am  convinced  that  we  have  obtained  them  by  attacking 
the  malady  wherever  we  find  it  vulnerable,  in  its  primordial 
cause — infection,  as  in  its  necessary  effects — poisoning,  fever, 
and  inanition. 


LECTURE   XXIY. 

AUTO-INTOXICATION  BY  BILE.     PATHOGENESIS  OF  JAUNDICE. 

The  elements  constituting  bile.  Experimental  studies  of  the  toxic  nature  of 
bilirubiu  and  the  biliary  salts.  How  the  greater  number  of  the  elements  of 
bile  become  inert  by  precipitation  in  the  digestive  tube.  The  role  of  the 
liver  as  a  protecting  agent  against  the  part  that  might  be  re-absorbed. 
When  bile  passes  into  the  blood,  the  white  connective  tissues,  by  fixing 
the  bilirubiu,  prevent  it  from  injuring  the  other  elements.  The  urine  then 
draws  it  off  little  by  little.  The  biliary  salts  are  gradually  eliminated  by 
the  urine.  The  sudden  injection  of  a  considerable  quantity  of  bile  into 
the  blood  kills  animals  without  producing  jaundice.  The  slow  injection  of 
the  same  quantity  of  bile  causes  jaundice  and  does  not  kill.  Influence  of 
biliary  retention  on  the  hepatic  cells  and  on  nutrition. 

BEFORE  concluding  the  study  of  intoxication  by  the  natural 
poisons  of  the  system,  I  will  discuss  poisoning  by  bile,  or  jaun- 
dice. This  is  a  question  that  I  have  already  touched  upon  in- 
cidentally when,  in  speaking  of  uraemia,  I  had  occasion  to  quote 
some  of  the  data  relating  to  the  poisonous  nature  of  bile.  When 
once  it  is  spread  over  the  surface  of  the  intestines,  bile  is  found 
to  be  under  very  different  conditions  than  when  it  is  in  the  liver. 
The  re-absorption  of  bile  takes  place,  no  doubt,  with  some  in- 
tensity in  the  duodenum,  but  it  is  principally  inoffensive  matter 
that  is  re-absorbed,  and,  moreover,  if  the  noxious  portion  of  the 
bile  is  re-absorbed  in  any  considerable  quantity,  it  is  again  stopped 
by  the  liver  and  rejected  into  the  intestines.  In  order,  there- 
fore, to  study  fully  the  toxic  effects  of  bile,  we  must  examine  it 
in  the  liver  at  the  moment  of  its  secretion. 

Bile  is  very  abundant,  being  almost  equal  in  quantity  to  the 
urine ;  its  secretion  is  over  800  cubic  centimetres  in  twenty-four 
hours;  and  it  may  even  amount  to  1200  and  1300  cubic  centi- 
metres. It  is  a  diffusible  liquid,  passing  b}'  means  of  exosmosis 
into  the  blood;  it  is  rich  in  solid  substances  (from  10  to  15  per 
cent.)  all  capable  of  dialysis.  Bile  does  not  contain  albumen  ; 
but  mucin  is  found  in  it,  and  this  gives  it  its  viscosity ;  it  also 
contains  cholesterin,  which  is  erroneously  considered  poisonous, 
as  we  find  considerable  quantities  in  atheromatous  abscesses  of 
(222) 


POISONOUS  QUALITIES   OF   BILIARY   DERIVATIVES.  223 

the  aorta  ;  olein,  margarin  ;  coloring  matter, — important  from  a 
toxic  point  of  view ;  the  biliary  salts  and  the  alkaline  soaps,  by 
means  of  which  the  cholesterin  is  held  in  solution. 

Of  the  various  coloring  substances,  bilirubin  is  the  only  one 
that  we  need  discuss;  the  others — bilifulvin,  biliverdin,  bili- 
fuscin,  biliprasin,  and  bilihumin — are  merely  derivatives  of  bili- 
rubin. Bilirubin  is  soluble  in  water  and  in  chloroform ;  it 
gives  rise  to  Gmelin's  reaction  when  treated  with  nitric  acid. 
This  coloring  matter  is  generally  precipitated  suddenly  in  the 
intestines,  on  contact  with  the  acid  cli3rme,  which  renders  it 
insoluble  and  prevents  it  from  being  re-absorbed.  We  must 
take  into  account  the  biliary  salts  whose  base  is  sodium,  which 
is  a  non-poisonous  base.  The  glycocholic  and  taurocholic  acids 
of  Lehman n,  still  known  as  cholic  and  choleic  acids,  are  very 
unstable.  Under  the  influence  of  potass  and  heat  they  generate 
cholalic  acid,  and,  besides  this,  the  first-named  gives  off  glyco- 
col,  and  the  second  taurin.  The  biliary  acids  are  also  trans- 
formed, under  the  influence  of  sulphuric  acid,  into  choloidic  acid 
and  into  glycocol  or  taurin, — a  reaction  which,  upon  contact 
with  certain  digestive  juices,  is  effected  in  the  intestines  as  in 
the  test-tube.  Finally,  the  cholalic  and  choloidic  acids  take  the 
form,  in  the  intestines,  of  an  insoluble  substance,  viz.,  dystysin, 
which  is  no  longer  injurious. 

The  coloring  matter  and  the  biliary  acids,  which  are  both 
poisonous,  becoming  thus  insoluble  in  the  intestines,  we  need 
not  wonder  that,  notwithstanding  the  quantity  of  bile  poured 
into  the  intestines  and  the  intensit}'  of  its  re-absorption,  no 
poisoning  takes  place,  even  when  the  kidney  is  only  slightly 
permeable.  But  these  transformations  are  neither  immediate 
nor  constant.  In  certain  persons  we  find,  even  near  the  anus, 
bilirubin  still  intact,  and  biliary  acids  that  have  not  undergone 
transformation,  owing  to  the  rapidity  and  intensity  of  the  con- 
tractions of  the  intestines. 

Even  in  a  normal  state  of  health  a  certain  quantity  of  the 
toxic  matter  may  be  re-absorbed  in  the  duodenum.  But  the 
liver,  as  Schiff  has  shown,  arrests  these  poisonous  substances 
and  restores  them  to  the  intestines  or  transforms  them  into 
harmless  matter. 


224  LECTURES  ON   AUTO-INTOXICATION. 

In  any  case,  the  reality  of  the  toxic  nature  of  bile,  which 
has  long  been  believed  in  by  the  medical  world,  has  recently 
been  experimentally  established.  According  to  my  experi- 
ments, from  4  to  6  cubic  centimetres  of  bile  are  required  to  kill 
in  convulsions  a  living  animal  weighing  1  kilogramme,  and,  since 
the  daily  secretion  of  bile  is  about  1000  cubic  centimetres,  we 
must  conclude  that  during  every  twenty-four  hours  a  man 
makes,  by  the  activity  of  his  liver  alone,  an  enormous  quantity 
of  poison, — enough  to  kill,  in  twenty-four  hours,  three  men  of  his 
own  weight,  1  kilogramme  producing  enough  to  kill  more  than 
2800  grammes  of  living  matter.  Man  forms,  in  eight  hours, 
enough  poison  to  kill  himself  simply  by  his  hepatic  secretion. 
Now,  in  twenty-four  hours  the  urine  does  not  eliminate  half  the 
quantity  necessary  to  poison  a  man ;  the  urine  of  two  days  and 
four  hours  would  be  required  in  order  to  do  this.  The  volume 
being  equal,  bile  is  nine  times  as  poisonous  as  urine ;  in  an  equal 
period  of  time  the  biliary  secretion  represents  a  degree  of  toxic 
power  six  times  as  great  as  the  urinary  secretion.  I  have 
shown  that  bile  decolorized  by  carbon  has  one-third  of  the  toxic 
properties  of  bile  in  its  natural  condition. 

This  leads  us  to  suspect  the  toxic  nature  of  bilirubin.  We — 
M.  Tap  ret  and  myself — have  demonstrated  it  by  an  intra-venous 
injection  of  this  substance  dissolved  in  water  by  means  of  a 
little  soda.  Bilirubin  kills  rabbits  in  a  dose  of  5  centigrammes 
per  kilogramme.  We  found,  moreover,  that  each  of  the  biliary 
salts  is  only  one-tenth  part  as  poisonous  as  bilirubin. 

The  urine  does  not  carry  away  the  whole  of  the  poisonous 
matter  secreted  by  the  liver,  therefore  the  greater  part  of  this 
substance  must  be  neutralized  in  some  part  of  the  body.  Even 
if  the  urine  owed  the  whole  of  its  poisonous  nature  to  bile,  the 
latter  would  have  had  to  lose  five-sixths  of  its  toxic  properties 
in  some  other  way. 

This  neutralization  is  effected  in  the  intestines,  in  the  liver, 
in  the  tissues,  and  in  the  blood. 

Schiff  thinks  that  bile  does  not  poison  us,  because  the  liver 
take.s  it  back  and  rejects  it,  to  take  it  back  and  reject  it  again, 
and  that  each  time  a  smaller  and  smaller  portion  is  absorbed. 
The  true  protection  seems  to  me  to  be  the  precipitation  of  the 


PROTECTIVE   ROLE   OF   THE   TISSUES   IN   JAUNDICE.  225 

poisonous  elements  of  the  bile, — i.e.,  the  coloring  matter  and  the 
salts, — which,  when  once  precipitated,  escape  from  absorption. 

I  think,  also,  that  the  tissues  play  a  certain  protective  r61e  : 
they  consume  and  transform  the  minute  portions  of  bile  which, 
having  been  absorbed,  have  penetrated  into  the  general  circula- 
tion ;  they  fix  the  bilirubin.  The  blood  consumes  the  biliary 
acids. 

Is  it  the  same  when  the  bile  is  re-absorbed  into  the  liver 
itself?  When,  in  consequence  of  an  osmotic  change,  the  bile 
passes  from  the  biliary  cell  into  the  blood-vessels,  the  flow  of 
bile  extends  to  the  general  circulation,  and  is  no  longer  confined 
to  one  region ;  the  protection  of  the  intestines  and  the  liver  is 
suppressed.  It  is  the  bile  in  its  entirety  that  passes  from  the 
liver  into  the  blood,  and  not  the  part — which  is  unimportant, 
from  a  toxic  point  of  view — which  was  re-absorbed  in  the  intes- 
tines. 

The  coloring  matter  and  biliary  acids  will  circulate  through- 
out the  body.  A  part  will  escape  through  the  kidneys,  but  the 
greater  part  goes  to  impregnate  the  tissues,  the  anatomical  ele- 
ments, the  normal  and  pathological  humors.  The  skin,  the  con- 
nective tissue,  the  hepatic  cells,  the  muscular  fibres,  the  vitreous 
bod}r,  all  the  epithelial  cells,  the  sj-novial  fluid,  and  the  serous 
cavities  are  penetrated  with  bile.  Upon  examination,  the  ana- 
tomical elements  give  two  reactions :  that  of  Gmelin  for  the  pig- 
ment and  of  Pettenkofer  for  the  acids.  This  is  what  is  asserted 
by  clinical  and  pathological  anatomy,  but  the  appearance  of  these 
gross  manifestations  of  the  passage  of  bile  into  the  blood  is 
not  immediate  ;  emotional  jaundice,  if  it  exist,  is  a  rare  excep- 
tion. When  we  are  quite  sure  of  the  precise  moment  of  the 
stoppage  of  the  bile,  as  in  hepatic  colic,  in  which  it  is  indicated 
by  pain,  we  may  easily  see  that  it  is  often  twentj'-four  hours,  or 
even  more,  before  the  icteric  tint  shows  itself  in  certain  mucous 
secretions  and  in  certain  parts  of  the  skin.  The  urine  is  colored 
more  quickly.  How  is  it  that  so -long  a  time  elapses  before  the 
tint  shows  itself  upon  the  person  himself?  This  fact  seems  to 
contradict  the  data  furnished  by  experiment. 

I  make  an  intra-venous  injection  of  bile  and  kill  the  animal 
in  a  few  minutes,  without  the  skin  having  taken  the  jaundiced 


226  LECTURES  ON    AUTO-INTOXICATION. 

tinge  or  the  urine  having  been  colored.  This  is  an  experimental 
fact  that  contradicts  clinical  experience.  It  has  even  been 
asserted  that  the  intra-veuous  injection  of  bile  cannot  produce 
jaundice.*  Feltz  and  Ritter  never  succeeded  in  obtaining  it. 

Vulpian  injected  250  cubic  centimetres  of  bile  into  a  dog 
slowly,  the  injection  lasting  three  days ;  the  animal  became 
icteric.  It  is  true  that  dogs  are  often  icteric  normally.  Never- 
theless, in  Yulpian's  experiment  the  tissues  and  organs  were 
tinged  with  bile,  and  the  jaundice  was  certainly  very  pronounced. 

It  is  because  bile  is  so  poisonous  that  a  sudden  injection  of 
bile  does  not  produce  jaundice ;  death  ensues  before  the  tissues 
have  had  time  to  become  colored.  When,  instead  of  bile,  a 
solution  of  bilirubin  only  is  injected,  the  five  centigrammes  of 
bilirubin  that  are  sufficient  to  kill  one  kilogramme  of  living 
animal  matter  are  also  sufficient  to  cause  intense  jaundice  during 
the  few  minutes  that  elapse  between  the  commencement  of  the 
injection  and  death.  When  the  bile  is  suddenly  introduced  into 
the  circulation,  the  coloring  matter  does  not  tinge  the  tissues. 
A  piece  of  white  silk,  quickly  plunged  into  icteric  urine  and 
washed  immediately,  is  scarcely  colored  ;  in  this  urine  still  more 
diluted  it  is  colored  in  proportion  to  the  duration  of  its  immer- 
sion, and  the  urine  is  discolored.  When  the  animal  is  suddenly 
poisoned,  we  must  consider  the  quantity  of  soluble  poison  that 
can,  at  a  given  moment,  produce  an  impression  on  the  nerve- 
cells,  also  the  time  necessary  for  the  fixation  of  the  pigment  on 
the  white  tendinous  and  aponeurotic  fibres,  etc.,  in  order  to  color 
them.  In  order  to  color  a  tissue,  time  is  necessary,  rather  than 
concentration  of  bile. 

Once  freed  from  its  coloring  matter,  bile  loses  part  of  its 
toxic  property ;  thus,  when  bile  is  injected,  if  the  injection  is 
sufficiently  slow,  the  white  fibres,  by  fixing  the  bilirubin,  pro- 
tect the  nerve-cells.  During  this  time,  the  biliary  salts  escape 
by  way  of  the  kidneys  or  are  consumed  in  the  blood.  We  may 

*  Vaughan  Harley  has  shown  (Brit.  Med.  Jour.,  Aug.,  1892)  that  in  jaundice, 
contrary  to  the  hitherto-entertained  pathological  doctrine,  the  bile  which  stains  the 
skin  and  discolors  the  urine  is  not  absorbed  into  the  general  circulation  by  the  blood- 
capillaries,  but  solely  by  the  lymphatic  system  of  vessels,  and  that  it  does  not  reach 
the  general  circulation  by  the  hepatic  veins,  but  by  the  thoracic  duct.  Where  the 
thoracic  duct  has  been  ligatured  no  bile  is  found  in  the  urine  or  blood.  A  similar 
view  is  held  by  Foster,  in  Text-book  of  Physiology,  p.  440.— T.  O. 


RENAL   PERMEABILITY   THE   SAFEGUARD   IN   JAUNDICE.          227 

thus,  both  experimentally  and  clinically,  obtain  icteric  colora- 
tion without  poisoning,  if  the  injection  or  re-absorption  be 
slow. 

Clinically  speaking,  if  all  the  bile  secreted  in  eight  hours 
were  introduced  suddenly  into  the  blood,  we  should  see  fatal 
nervous  effects  produced  immediately.  But  as  elimination  is 
incessantly  being  effected  through  the  kidneys,  and  as  the 
fibres  of  the  connective  tissue  are  being  incessantly  colored, 
whilst  the  blood  re-absorbs  only  gradually,  nervous  accidents 
are  thus  averted.  The  tissues  serve  to. protect  the  organism 
against  certain  poisons.  Experience  shows  us  that  the  most 
intense  form  of  jaundice,  viz.,  black  jaundice,  does  not  kill,  pre- 
cisely because  the  coloring  matter,  which  is  ten  times  more 
poisonous  than  the  biliary  salts,  becomes  fixed. 

Thus,  in  addition  to  the  protection  afforded  by  the  liver  and 
intestines,  the  system  finds  a  protection  against  biliary  poisoning 
owing  to  tissues  which,  as  regards  functional  importance,  occupy 
the  lowest  rank  among  the  anatomical  elements,  drawing  off 
from  the  blood  the  greater  portion  of  the  coloring  matter,  in 
order  to  absorb  it  themselves.  Lastly,  the  kidneys  also  take 
part  in  the  elimination  of  the  biliary  acids  ;  we  find,  in  the  urine 
of  those  suffering  from  jaundice,  sulphur  incompletel}-  oxidized, 
or  in  the  form  of  sulphur  compounds;  this  sulphur  is  derived 
from  the  taurin,  and  should  be  eliminated  by  the  intestines. 

Notwithstanding  this  elimination  through  the  kidneys,  part 
of  the  biliary  salts,  passing  through  the  system,  affects  the  blood- 
corpuscles,  the  hepatic  cells,  the  muscular  fibre,  the  epithelial 
elements,  and  according  as  the  kidne}7  performs  more  or  less 
perfectly  its  work  of  elimination  it  causes  more  or  less  rapid 
destruction  of  these  elements.  Sometimes  only  disassimilation 
is  merely  hastened,  and  emaciation  is  then  rapid.  Sometimes 
disassimilation  is  so  rapid  that  the  oxygen  that  is  available 
ceases  to  be  available  for  combustion  ;  fatty  degeneration  then 
results  from  the  persistence  of  one  of  the  products  of  the 
disintegration  of  the  nitrogenous  matter. 

Moreover,  the  retention  of  the  biliary  acids  acts  upon  the 
hepatic  cell,  which  itself  undergoes  fatty  degeneration.  Then  a 
new  effect  is  produced,  the  functional  consequence  of  acute 


228  LECTURES   ON   AUTO-INTOXICATION. 

atrophy  of  the  liver,  viz.,  suppression  of  the  final  processes  of 
disassimilation. 

The  substances  disassimilated  no  longer  undergo  all  the  met- 
amorphoses to  which  the}'  are  normally  subjected  in  the  liver. 
The  matter  that  is  decomposed  no  longer  takes  the  form  of  ex- 
crement ;  the  albuminoid  substances  remain  colloid,  instead  of 
being  crystalloid  and  therefore  dialysable.  Urea,  which  is  an 
eminently  diuretic  substance,  diminishes ;  the  result  is  a  diminu- 
tion of  renal  activity.  Now,  this  is  a  new  danger,  a  fresh  obstacle 
to  elimination.  Often  also  the  kidney  is  affected  on  its  own 
account  by  the  cause  that  has  produced  jaundice, — an  infectious 
malady,  for  example.  But  this  has  to  do  with  quite  another  kind 
of  poisoning.  The  liver  no  longer  makes  bile,  and  yet  it  is  not 
acholia  that  kills  the  patient.  The  poisoning  is  due  to  all  the 
causes  that  are  poisoning  the  system  when  the  kidneys  no  longer 
act,  and  also  to  those  substances  that  are  ordinarily  transformed 
by  the  liver  into  excrementitious  mattei*. 

The  greatest  danger  in  jaundice  is  renal  impermeability.  On 
the  other  hand,  severe  cases  of  jaundice  may  be  cured  if  the 
kidneys  remain  permeable. 


LECTURE  XXV. 
MALIGNANT  JAUNDICE  :  AGGRAVATED  JAUNDICE. 

Importance  of  the  functional  and  anatomical  soundness  of  the  kidneys  from  the 
point  of  view  of  the  cure  of  jaundice.  The  various  causes  that  often  render 
the  kidneys  unhealthy  in  jaundice. Consequences  of  the  tissues  being  im- 
pregnated with  bile.  The  diminution  and  then  the  suppression  of  the  hepatic 
functions  :  the  influence  of  the  stoppage  of  the  functions  of  the  liver  on 
assimilation  and  disassimilation.  Accumulation  in  the  blood  of  the  waste 
products  of  nutrition  incompletely  transformed  and  unfit  for  excretion.  To 
auto-intoxication  by  natural  poisons  succeeds  poisoning  by  anomalous 

poisons. The  relation  of  the  various  accidents  attendant  upon  aggravated 

jaundice  :  cholaemia,  acholia,  uraemia. The  extremely  poisonous  nature 

of  the  urine  of  patients  suffering  from  jaundice,  so  long  as  the  kidneys  are 
permeable.  Importance  of  polyuria  in  the  prognosis  of  jaundice. Distinc- 
tion between  the  aggravated  forms  of  jaundice  and  the  particular  malady 
called  malignant  jaundice,  or  acute  yellow  atrophy  of  the  liver,  which  is, 
perhaps,  caused  by  an  infective  agent,  and  may  be  developed  without 
jaundice. 

FROM  what  I  said  in  the  preceding  lecture  on  the  subject  of 
the  causes  of  the  poisoning  in  jaundice,  I  showed  that  there  are 
two  poisons  in  bile, — the  biliar}-  salts,  which  have  alwa3*s  been 
recognized  as  poisons,  and  a  substance  which,  up  to  the  present, 
has  not  been  appreciated,  from  a  toxic  point  of  view,  viz.,  the 
coloring  matter.  This  is,  I  think,  anew  revelation  in  pathology. 
I  wish  also  to  call  particular  attention  to  the  fact  that,  although 
in  jaundice  a  considerable  quantity  of  poison  enters  into  the 
system,  nevertheless,  in  the  great  majority  of  cases,  this  intro- 
duction of  poison  is  not  followed  by  death,  as  the  organism  is 
doubly  protected. 

In  the  first  place,  the  kidneys  cany  off  part  of  the  pigment 
and  the  biliary  acids  and  their  derivatives ;  therefore  the  urine 
becomes  poisonous,  and  I  have  found  that  jaundiced  urine  kills 
in  the  proportion  of  ten  and  even  seven  cubic  centimetres  per 
kilogramme  of  the  animal.  On  the  other  hand,  the  fibres  of 
the  connective  tissue  fix  the  most  important  of  the  poisons  of 
bile,  the  coloring  matter.  The  tissues,  by  becoming  colored,  with- 
draw from  the  circulation,  in  increasing  proportion,  this  poison, 

(229) 


230  LECTURES  ON   AUTO-INTOXICATlOtf. 

and  exercise  gradually  a  sort  of  condensing  power.  Neverthe- 
less, notwithstanding  this  double  protection,  we  observe,  even  in 
mild  cases  of  jaundice,  as  the  first  signs  of  poisoning, — slowing 
of  the  pulse,  pruritus,  nasal  haemorrhages,  and  rapid  emaciation. 
If  the  kidneys  become  less  permeable,  the  conditions  of  poison- 
ing increase.  Now,  the  kidneys  often  act  insufficiently  in  jaun- 
dice, frequently  through  a  cause  that  is  independent  of  and 
anterior  to  the  jaundice  itself.  Nephritis  may  supervene  and 
aggravate  the  malady,  resulting  often  from  the  same  cause  that 
has  produced  the  jaundice, — an  infective  agent.  The  liver  also 
may  become  disordered,  like  the  spleen  and  the  kidnej^s,  owing 
to  infectious  agencies  having  reached  it.  Lastty,  the  impermea- 
bility of  the  kidneys  may  be  the  consequence  of  the  jaundice 
itself  altering  the  epithelial  cells.  The  consequence  of  the  im- 
permeability of  the  kidney  is  the  retention  of  the  coloring  mat- 
ter and  of  the  biliary  salts.  The  biliary  impregnation  of  the 
red  corpuscles,  the  hepatic  cells,  muscular  fibre,  epithelial  cells, 
and  the  vascular  membranes  causes  destructive  modifications  in 
all  these  elements. 

Disassimilation  is  more  rapid  or  is  affected  by  anomalous 
processes.  The  destruction  of  the  cellular  elements  takes  place 
either  totally  or  by  fatty  degeneration.  We  note  a  diminution 
in  the  number  of  corpuscles,  which  are  swollen  and  spherical. 
The  serum  contains  haemoglobin  in  solution,  not  modified.  The 
heart,  which  is  altered  in  its  structure,  loses  some  of  its  energy ; 
its  beats  are  at  first  slower,  and  then  feebler  and  more  frequent. 

Then  atrophy  of  the  liver  may  set  in.  Atrophy  of  the  liver 
is  characteristic  of  one  form  of  jaundice,  but  does  not  belong 
exclusively  to  it,  and  it  may  occur  even  in  cases  which  pass 
from  the  benign  to  the  grave  form.  We  note  at  first  a  gradual 
diminution,  and  finally  suppression,  of  the  hepatic  function, 
which  consists  in  transforming  the  materials  of  disassimilation, 
as  well  as  those  of  assimilation. 

We  must  not  forget  that  the  liver  has  a  double  function.  On 
the  one  hand,  it  has  to  develop  the  matter  absorbed  from  the  intes- 
tines— sugar,  for  instance — in  order  to  form  glycogen  ;  if  this 
work  cease,  the  organism  is  deprived  of  a  substance  that  is 
indispensable  to  it.  On  the  other  hand,  the  liver  has  to  com- 


CONSEQUENCES   OP    SUPPRESSED   HEPATIC   FUNCTION.  231 

plete  the  development  of  the  materials  produced  \>y  disassimila- 
tion ;  before  they  pass  inta  the  excretory  passages,  colloids 
should  be  converted  into  crystalloid  dialyzable  material. 

Thus,  when  atrophy  of  the  liver  sets  in,  the  repair  of  the  waste 
of  tissue  is  interfered  with,  and  there  is  an  accumulation  of  the 
matter  produced  by  disassimilation,  which  has  not  been  able  to 
pass  into  the  state  for  being  excreted.  The  proteid  substances 
no  longer  reach  the  state  of  urea;  therefore,  the  urea  diminishes. 
Now,  this  is  the  most  important  physiological  diuretic,  forcing 
the  water  to  pass  away  through  the  kidneys  and  to  carry  off  at 
the  same  time  the  other  solid  excrementitious  matter. 

While  these  modifications  are  taking  place  in  the  natural 
chemistry  of  the  liver  parallel  chemical  modifications  of  the 
blood  are  also  going  on.  An  accumulation  of  leucin,  tyrosin, 
xanthin,  and  hypoxanthin  is  produced  in  the  blood  and  in  the 
tissues.  These  same  substances  consequently  appear  in  the 
urine ;  and  besides  other  substances,  the  greater  number  of 
which  are  little  known,  we  find  in  the  urine  imperfectly-formed 
albumens,  which  have  not  the  normal  point  of  coagulation  by 
heat,  and  which  act  differently  when  treated  by  chemical  reagents. 
The  kidney  is  not  constructed  for  the  elimination  of  these 
bodies,  but,  nevertheless,  they  force  their  way  through  the  renal 
barrier. 

The  biliary  function,  also,  of  a  liver  which  is  being  destroyed 
by  jaundice  is  soon  diminished  or  suppressed.  The  liver  be- 
comes incapable  of  forming  the  pigment  and  the  biliary  acids,  so 
that  the  jaundice  itself  may  diminish,  and  even  disappear;  the 
biliary  pigment  decreases  in  the  urine,  and  at  a  given  moment, 
in  patients  that  were  at  first  poisoned  by  bile,  biliary  poisoning 
is  suppressed.  We  no  longer  find  in  the  urine  biliary  acids 
or  compounds  of  sulphur,  or  the  incompletely-oxidized  sulphur 
derived  from  them. 

When  we  administer  to  a  patient  suffering  from  acute  atropl^y 
of  the  liver  a  substance  which,  tinder  normal  conditions,  should 
undergo  certain  metamorphoses  in  the  liver, — substances  which, 
like  naphthalin,  fix  the  sulphur  radicals, — we  find  that  the 
elaboration  of  this  body — say,1  naphthalin — is  not  accomplished 
according  to  the  normal  processes.  Instead  of  being  eliminated 


232  LECTURES  ON   AUTO-INTOXICATION. 

in  the  form  of  naphthyl-sulphite  of  soda,  it  is  found — in  cholera 
patients,  for  instance — in  the  urine,  in  a  form  which  is  as  yet 
undefined,  notwithstanding  M.  Rosenstiehl's  researches ;  it  gives 
rise  to  a  particular  coloring  matter,  of  a  purple-violet  tint, 
similar  to  that  of  permanganate  of  potash.  I  have  observed  this 
coloration,  which  is  due  to  an  anomaly  in  the  elaboration  of  the 
naphthalin,  in  acute  atrophy  of  the  liver  and  in  .two  cases  of 
typhoid  fever.  Thus,  when  the  liver  is  destroyed,  disassim- 
ilated  substances  are  defectively  elaborated ;  the  chemistry  of 
malignant  jaundice  confirms  this,  and  this  particular  case  of  the 
anomalous  elaboration  of  naphthalin  in  acute  atrophy  of  the 
liver  and  cholera  furnishes  a  still  better  demonstration. 

Besides  the  disorders  resulting  from  the  suppression  of  the 
hepatic  functions  in  malignant  jaundice  the  kidneys,  if  not  already 
disordered,  soon  become  so.  In  the  same  way  that  lead,  silver, 
mercury,  and  cantharides,  when  being  eliminated,  cause  true 
toxic  nephritis,  so  do  the  biliary  poison  and  the  poisons  fabri- 
cated in  a  secondary  manner,  by  imperfect  disassimilation,  during 
their  elimination,  produce  renal  changes.  This  is,  then,  a  fresh 
hindrance  to  renal  ejection,  and  a  new  cause  of  the  retention  of 
poisons  in  the  system.  Lastly,  the  vessels  also  become  affected ; 
extravasations  are  produced,  and  in  some  cases,  which  cannot  be 
called  exceptional,  renal  haemorrhage  still  further  increases  the 
impermeability  of  the  kidneys.  Thus,  while  the  chances  of 
biliary  poisoning  diminish,  causes  of  secondary  poisoning  appear, 
which  continually  increase  in  consequence  of  the  renal  imperme- 
ability, the  anomalous  elaboration  of  the  liver,  and  the  alteration 
of  all  the  cells  of  the  body. 

Auto-intoxication  by  natural  poisons  is  succeeded  by  self- 
poisoning  by  other  morbid  poisons.  If  objections  are  raised  to 
this  singular  complexity  of  the  phenomena,  if  I  am  blamed  for 
substituting  for  the  too  simple  and  natural  idea  of  the  patho- 
genesis  of  the  serious  accidents  attendant  upon  jaundice,  owing 
to  the  action  of  the  biliary  salts,  that  of  the  train  of  processes 
which  take  place  one  after  the  other  in  natural  sequence,  I  shall 
answer  that  not  a  single  link  in  this  chain  can  be  shown  to  be 
false,  and  that  the  truth  of  each  separate  detail  can  be  established. 
Only  the  degree  of  their  subordination  is  left  in  doubt. 


RENAL  PERMEABILITY  THE  SAFEGUARD  IN  JAUNDICE.    233 

Now,  with  regard  to  jaundice  that  has  become  serious,  we 
are  obliged  to  appeal  to  this  succession  of  the  various  processes. 
I  cannot  affirm  positively  that  such  and  such  a  succession  is  the 
absolute  order  of  facts,  but  I  firmly  believe  that  they  all  play  an 
important  part,  and  I  am  inclined  to  believe  that  the  order  of 
complications  is  as  follows  :  Biliary  poisoning  (cholaemia)  ;  cell- 
degeneration,  particularly  alteration  of  the  hepatic  cells;  atrophy 
of  the  liver  and  suppression  of  its  functions  (acholia), — renal 
changes  from  various  causes,  ending  in  renal  inadequacy;  Lastly, 
self-poisoning,  of  a  mixed  nature,  through  acholia, — i.e.,  through 
the  retention  of  anomalous  toxic  products;  and  through  uraemia, 
— i.e.,  through  the  non-elimination  of  the  normal  toxic  products, 
which  should  be  carried  off  by  the  urine. 

This  uraemic  element  cannot  alwaj-s  be  compared  with  ordi- 
nary uraemia ;  it  cannot  be  uraemia  from  an  alimentary  cause, 
the  patients  being  scarcely  nourished  at  all ;  nor  can  it  be  poison- 
ing from  re-absorption  of  bile,  since  the  latter  ceases  to  be 
secreted ;  the  putrefactions  of  intestinal  origin  certainty  con- 
tribute to  it  as  one  cause,  but  it  is  principal!}*  a  poisoning  by 
the  normal  or  abnormal  refuse  throwli  off  by  intense  disassimila- 
tion,  setting  free  potass, — which  is  quite  capable  of  poisoning 
and  of  causing  convulsions  in  a  large  number  of  cases, — and  also 
organic  matter  incompletely  elaborated.  Thus,  the  greatest 
danger  in  severe  jaundice  is  the  impermeability  of  the  kidnej-s. 
If  the  kidneys  remain  permeable,  the  patients  discharge  urine 
that  is  intensely  poisonous,  and  which  has  a  great  tendency  to 
cause  convulsions.  This  urine,  even  when  decolorized  by  carbon, 
retains  its  convulsive  power;  it  is  sufficiently  powerful  to  kill 
animals  in  opisthotonos,  as  if  they  were  poisoned  by  the  potass 
that  has  been  sent  in  excess  into  the  blood  through  the  exag- 
gerated disassimilation  of  the  tissues.  If  the  kidneys  are  no 
longer  permeable,  the  urine  will  no  longer  have  this  convulsive 
power,  but  the  patient  will  be  poisoned  and  have  the  con- 
vulsions. 

As  long  as  renal  impermeability  is  not  manifested,  the  prog- 
nosis may  be  reserved  in  severe  attacks  of  jaundice,  and  complete 
recovery  is  possible.  In  certain  cases,  after  having  observed 
the  hepatic  dullness  diminish  every  day,  we  then  see  it  return  by 


234  LECTURES  ON   AUTO-INTOXICATION. 

degrees  to  its  original  limits,  showing  that  the  liver  has  regained 
its  volume  in  the  space  of  a  few  weeks  or  a  few  days.  I  have 
personally  remarked  two  instances  of  this  kind.  The  severe 
jaundice  was  not  then  complicated  by  renal  lesions  ;  the  polyuria 
remained  constant,  and  from  three  to  four  litres  of  urine  were 
secreted  daily.  Is  all  that  I  have  said  applicable  to  the  partic- 
ular malady  which  Rokitansky  has  called  acute  }rellow  atrophy 
of  the  liver?  to  the  form  of  severe  jaundice  described  by  Ozanam  ? 
to  the  typhoid  jaundice  of  Lebert?  to  the  essential  hsemorrhagic 
jaundice  of  Monneret,  or  the  essentially-grave  jaundice  of  Genou- 
ville  ?  I  do  not  think  so.  What  I  have  said  applies  to  simple 
attacks  of  jaundice  that  have  become  severe ;  moreover,  these 
are  perhaps  the  most  common  class. 

According  to  Frerichs,  the  primordial  cause  is  atrophy  of 
the  liver,  which,  by  vitiating  the  elaboration  of  the  various 
kinds  of  matter,  produces  all  the  other  complications.  Other 
hypotheses  have  been  proposed.  We  need  not  discuss  jaundice 
proceeding  from  the  suppression  of  the  hepatic  function,  no 
more  than  jaundice  from  polycholia  or  from  too  great  activity 
of  the  hepatic  function,  the  jaundice  in  these  cases  being  only 
slight,  of  short  duration,  or  absent.  At  least,  there  have  been 
as  many  theories  formed  about  severe  jaundice  as  about  uraemia. 

Buhl's  theory  is,  that  severe  jaundice  is  the  result  of 
cerebral  oedema ;  that,  elimination  of  water  by  the  bile  being 
suppressed,  hydraemia  ensues,  and  then  cerebral  oedema.  Can 
we  admit  that  the  800  or  1200  grammes  of  water  in  the  quantity 
of  bile  formed  daily  can  produce  such  effects  when  we  know  that, 
normally,  the  intestines  re-absorb  half  or  two-thirds  of  this 
water? 

Uraemia  alone  is  to  be  considered  the  cause,  according  to 
another  opinion.  I  have  taken  it  into  account,  as  you  know,  but 
we  can  only  trace  its  terminal  complications.  There  onty,  then, 
remains  acholia, — the  suppression  of  the  part  played  by  the  liver 
in  disassimilation ;  this  is  French's  theory,  and  I  believe  it  to 
be  the  correct  one. 

But  what  can  produce  the  atrophy  of  the  liver?  Everything 
tends  to  show  that  it  is  the  consequence  of  a  general  infective 
malady,  not  only  because  infectious  agents  have  been  found  in 


ACUTE  ATROPHY  OP  THE  LIVER,  AN  INFECTIVE  PROCESS.   235 

the  fluids  and  the  tissues,  but  because  at  the  same  time  we  find 
fever,  purpura,  a  polymorphous  erythema,  scarlatiniform,  cir- 
cinate,  and  globular  eruptions  on  the  skin,  the  pharynx,  and  the 
palate,  and  because  an  acute  nephritis  exists,  with  parallel 
determinations  to  the  various  viscera. 

Jaundice  does  not  necessarily  supervene  in  acute  yellow 
atrophy  of  the  liver,  but  it  may  form  a  connecting  link  between 
the  destruction  of  the  hepatic  cells  and  .the  appearance  of  a 
nephritis,  which  adds  to  the  symptomatic  list  its  own  contingent 
of  accidents  traceable  to  uraemia.  The  study  of  severe  jaundice 
thus  serves  as  an  introduction  to  the  study  of  poisoning  by 
anomalous  products. 


LECTURE  XXYI. 
THE  Toxic  NATURE  OF  PATHOLOGICAL  URINES. 

Causes  of  death  in  infectious  diseases.  Examination  of  the  poisons  in  the  tissues 
of  animals  that  have  died  from  infection.  The  toxic  nature  of  the  urine  in 
tetanus.  Special  characteristics  of  the  toxicity  of  the  urine  in  fevers ;  con- 
vulsive properties.  The  part  played  by  poisoning  in  the  ataxo-adynarnic 
accidents  of  fevers  and  in  the  death-struggle. 

WE  know  that  in  the  course  of  infectious  diseases  there  exists 
a  perversion  of  the  nutritive  processes,  more  particularly  in  the 
function  of  the  liver-cells.  Under  the  influence  of  the  disease 
we  note  the  appearance  in  the  urine  of  anomalous  material,  the 
products  of  imperfect  disassimilation,  colloid  substances,  and 
modified  albumens.  We  find  drugs  undergo  unusual  trans- 
formations, naphthalin,  for  instance,  being  eliminated  without 
having  entered  into  combination  with  sulphur.  Some  of  these 
anomalous  products  may  be  poisonous,  but  this  is  only  a  matter 
of  conjecture,  requiring  demonstration.  This  task  is  not  an  easy 
one,  and  often  ends  in  a  negative  or  doubtful  -result. 

I  have  long  endeavored  to  find  the  substance  which  causes 
death  in  infectious  diseases.  If,  in  certain  cases,  death  may  be 
attributed  to  the  withdrawal  of  oxygen  from  the  blood,  as  in 
charbon ;  to  capillary  obstructions  hi  the  more  important  organs ; 
to  septic  foci  being  established  by  the  infectious  agents  passing 
out  of  the  vessels,  the  explanation,  in  the  majority  of  cases,  lies 
in  poisoning.  I  have  found  hardly  any  trace  of  those  poisonous 
substances  that  are  well  known,  especially  in  infections  of  diges- 
tive origin, — surface  infections.  I  found  that  the  alkaloids  were 
increased,  but  that  they  could  only  account  for  a  very  small  part  of 
the  auto-intoxication.  I  have  searched  for  this  poison  in  gaseous 
gangrene.  Charrin  has  also  endeavored  to  find  it  while  studying 
the  form  of  septicaemia  that  will  in  future  bear  his  name. 

Extracts  were  taken  from  all  the  organs  of  five  animals  that 
had  died  of  septicaemia.  These  extracts  were  injected  into 
healthy  animals  and  produced  poisoning,  but  with  extracts  from 
(236) 


ANIMAL   ALKALOIDS   IN    HEALTH   AND   DISEASE.  237 

the  organs  of  healthy  animals  we  also  obtain  poisoning.  Does 
not  the  destruction  of  the  anatomical  elements  allow  substances 
to  become  free  that  are  held  in  the  living  cells  by  the  forces  of 
tension  ?  The  normal  poisons  have  thus  prevented  the  discovery 
of  the  anomalous  poison.  Amongst  the  substances  that  may  be 
suspected  we  have  particularly  studied  the  alkaloids.  We  have 
extracted  alkaloids  from  the  bodies  of  animals  that  have  died 
of  infectious  diseases ;  but  we  also  find  alkaloids  in  the  tissues 
of  healthy  animals,  although,  perhaps,  in  smaller  quantities. 
However,  the  quantity  of  alkaloids  extracted  from  the  bodies  of 
five  animals  that  had  died  of  septicaemia  was  not  sufficient  to 
produce  poisoning.  We  have  not,  therefore,  succeeded  in  finding 
the  morbid  poison  that  kills  in  infectious  diseases,  but  these 
negative  results  do  not  alter  the  fact  that  we  must  admit  the 
existence  of  such  a  poison  in  these  cases.  How,  for  instance, 
can  we  explain  the  fact  that  gaseous  gangrene,  which  is  so  emi- 
nently infectious,  but  which  only  produces  local  anatomical 
injury,  without  embolism  or  any  inflammatory  process,  can 
cause  death,  if  it  is  not  that,  simultaneously  with  the  production 
of  oedema,  a  poison  is  fabricated  which  kills  the  higher  elements 
of  the  system  ?  This  is  mere  hypothesis,  it  will  be  said.  Yes, 
but  hypothesis  that  is  almost  necessary. 

Not  having  been  able  to  select  one  single  poisonous  substance 
that  could  really  be  considered  capable  of  producing  the  effects 
referred  to,  I  endeavored  to  study  the  poisonous  element  as  a 
whole,  taking  all  the  poisonous  substances  in  the  eliminating 
liquid, — the  urine.  By  proceeding  in  this  manner,  I  arrived 
at  results  that  seemed  to  me  to  be  convincing. 

A  patient  attacked  with  tetanus  passed  no  urine  for  two 
days.  M.  Labbe  collected  the  urine  when  it  re-appeared.  On 
being  injected  into  the  veins  of  an  animal,  it  produ<  .•<!  mild 
tremors  after  the  sixth  cubic  centimetre  ;  myosis  appeared  ;  the 
pupils  were  punctiform  at  ten  cubic  centimetres.  From  t\v»-lvr 
cubic  centimetres  there  were  violent  tonic  spasms  and  convul- 
sions up  to  the  thirty-fourth  cubic  centimetre;  death  thru  m- 
sued  from  opisthotonos.  Is  not  this  almost  a  complete  repro- 
duction of  the  symptoms  of  tetanus?  We  then  thought  that 
the  urine  contained  a  convulsive  poison,  which  was  the  cause 


238  LECTURES   ON   AUTO-INTOXICATION. 

of  the  tetanic  convulsions.  We  were  half  inclined  to  see  in 
this  the  confirmation  of  the  infectious  nature  of  tetanus.  This 
theory  was  very  tempting.  But  when  we  studied  the  toxic 
properties  of  the  urine  in  pneumonia  in  six  cases,  we  found 
at  once  that  it  is  more  poisonous  than  normal  urine ;  it  is 
capable  of  killing  in  the  proportion  of  nineteen  cubic  centi- 
metres per  kilogramme  of  the  animal,  as  a  minimum,  the  average 
proportion  being  thirty-eight  cubic  centimetres.  We  observe  in 
the  animal  the  ordinary  signs  of  poisoning  by  normal  urine, — 
myosts  and  lowering  of  temperature ;  but,  besides  these  symp- 
toms, we  get  tonic  convulsions  absolutely  similar  to  those  pro- 
duced by  the  urine  of  a  patient  suffering  from  tetanus,  spasms 
with  lasting  muscular  rigidity,  and,  finally,  death  from  opisthoto- 
nos.  The  urine  of  patients  suffering  from  pulmonary  spleniza- 
tion  killed  animals,  when  injected  in  quantities  of  twenty-two  cubic 
centimetres,  with  the  same  convulsions.  In  typhoid  fever,  at  its 
commencement,  before  intestinal  antiseptic  action  has  yet  been 
effected,  I  have  seen  the  urine  produce  only  those  toxic  phe- 
nomena that  belong  to  normal  urine, — no  convulsions,  very  little 
pupillary  contraction,  narcosis  ;  death  ensues  at  fifty,  sixty,  and 
seventy  cubic  centimetres. 

In  lead  poisoning,  sixty-six  cubic  centimetres  of  urine  per 
kilogramme  have  produced  death  without  convulsions.  In  leu- 
cocythaemia  the  urine  has  caused  death  in  convulsions  at  fifteen 
cubic  centimetres.  The  urines  of  those  suffering  from  jaundice 
cause  death  with  convulsions ;  the  fatal  result  might  in  this  case 
be  attributed  to  the  substances  of  biliary  origin,  the  acids,  or  the 
coloring  matter ;  but  I  have  reason  to  think  that  death  is  due  to 
another  cause.  The  urine  of  albuminuric  patients  not  suffering 
from  uraemia  causes  death  at  fifty-four  cubic  centimetres  without 
convulsions.  The  urine  of  those  attacked  with  uraemia  is  no 
longer  poisonous. 

From  all  these  experiments  it  follows  that  in  certain  chronic 
diseases  the  toxic  nature  of  the  urine  is  the  same  as  when  it  is 
in  a  normal  condition,  and  that  the  symptoms  are  the  same  as 
those  produced  by  normal  urine ;  but  in  the  greater  number  of 
pathological  urines,  and  in  that  of  all  feverish  diseases,  we  find  an 
increase  in  the  normal  degree  of  toxicity,  and  also  new  toxic 


CONVULSIVE   PROPERTY   OF    FEBRILE    URINES.  239 

properties,  especially  the  power  of  producing  convulsions.  The 
urine  of  fever  patients  has  all  the  characteristics  of  normal 
urine,  with  less  somnolence  and  with  the  addition  of  convulsions. 
The  convulsive  tendency  is  no  doubt  present  in  normal  urine, 
but  as  long  as  the  convulsive  poison  and  the  narcotic  poison  are 
in  conjunction  the  latter  annihilates  the  former.  It  is  possible 
that  normal  urine  might  be  capable  of  producing  convulsions  if 
the  narcotic  poison  were  withdrawn.  Thus,  the  injection  of  the 
urine  of  those  suffering  from  disease  produced  neither  the  repe- 
tition of  the  symptoms  of  the  disease  nor  4he  reproduction  of 
the  disease  itself.  Nevertheless,  I  once  found  that  the  urine  of 
a  patient  suffering  from  phthisis  produced  tuberculosis.  Lan- 
douzy  quotes  a  similar  case,  and  Toussaint  also.  Before  that 
occurred,  he  had  observed  the  reproduction  of  charbon  by  inoc- 
ulation with  the  urine,  and  Charrin  succeeded  in  reproducing  his 
septicaemia  by  the  same  means.  But  we  reproduce,  by  the  injec- 
tion of  urine,  those  infectious  diseases  that  can  be  transmitted  to 
animals,  and  in  which  the  infectious  agents  are  eliminated  through 
the  kidneys.  What  I  thought  to  obtain  by  the  injection  of  these 
pathological  urines  was  not  the  transmission  of  the  disease,  but 
the  reproduction  of  some  predominating  symptom.  I  did  obtain 
an  anomalous  symptom,  but  this  was  produced  indiscriminately 
by  the  urine  of  tetanus  and  that  of  pneumonia.  In  the  case  of 
diseases  that  are  not  infectious,  or  those  in  which  the  microbes 
are  not  eliminated  through  the  kidneys,  how  can  we  explain  the 
greater  toxicity  of  the  urine  and  that  special  convulsive  property 
which  we  find  is  common  to  nearly  all  febrile  or  consumptive 
diseases  ? 

Has  the  disease,  by  perverting  nutrition,  generated  poisonous 
substances?  In  pneumonia,  is  some  alkaloid,  or  other  poison 
formed  ?  This  question  is  at  present  unsolvable.  Moreover,  if 
we  admit  that  special  toxic  substances  are  formed  by  the  disease, 
how  can  we  explain  the  fact  that  all  diseases  shall  produce  the 
same  convulsive  poison?  Another  hypothesis  is  that  the  patho- 
logical urines  owe  their  toxic  nature  to  certain  normal  poisons 
produced  in  superabundant  quantities.  Several  substances  pro- 
duced by  normal  disassimilation  may  cause  convulsions.  If 
alimentation  is  suppressed  in  feverish  diseases,  disassimilation  is 


240  LECTURES   ON   AUTO-INTOXICATION. 

increased.  The  weight  of  the  body  sometimes  diminishes  several 
kilogrammes  in  twenty -four  hours.  Now,  the  destruction  of  the 
tissues  sets  free  potass,  a  substance  that  causes  convulsions.  In 
typhoid  fever  the  urine,  which  is  only  slightly  toxic  at  first,  when 
matter  is  being  slowly  destroyed  and  the  weight  of  the  patient 
is  scarcely  diminished,  becomes  decidedly  poisonous  at  the  period 
of  convalescence,  when  rapid  emaciation  takes  place.  This  is 
one  argument  in  favor  of  the  hypothesis  in  question. 

The  coloring  matter  is  increased  in  the  urine  of  fever  patients ; 
for  instance,  from  six  to  sixty  and  eighty  in  twenty -four  hours. 
Now,  highly-colored  urine  causes  contraction  of  the  pupil  and 
convulsions;  on  being  decolorized  by  charcoal,  they  lose  their 
convulsive  property.  However,  the  convulsive  power  of  certain 
pathological  urines  does  not  disappear  from  them  under  discolor- 
ation, which  proves  that,  in  these  cases,  the  convulsions  are  due, 
to'a  large  extent,  at  least  to  potass,  and  not  exclusively  to  convul- 
sive organic  matter.  Is  it  not  a  striking  fact  that  febrile  urine, 
in  which  the  coloring  matter  is  from  ten  to  twenty  times  as  abun- 
dant as  in  normal  urine,  becomes  so  intensely  convulsive  ?  We 
also  note  in  fever  a  diminution  in  the  salts  of  alimentary 
origin,— chloride  of  sodium,  for  instance.  Potass,  on  the  other 
hand,  is  doubled  or  trebled.  In  short,  then,  what  fever  does  is 
to  pour  in  excess,  into  the  blood  and  the  urine,  potass  and  color- 
ing matter,  or  at  least  toxic  substances  which  are  habitually  asso- 
ciated with  coloring  matter.  Now,  potass  and  coloring  matter 
are  powerfully  convulsive ;  I  am,  therefore,  inclined  to  think  that 
the  urine,  in  acute  diseases,  owes  its  toxicity  not  to  a  special 
poison,  but  to  certain  normal  poisons  in  excessive  quantities. 
Febrile  urine  produces  the  same  phenomena  as  normal  urine, 
only  more  quickly, — myosis,  polyuria,  lowering  of  temperature. 
Somnolence  appears  very  tardily ;  the  effect  of  the  narcotic  sub- 
stance is  diminished,  it  being  overpowered  by  the  convulsive 
poison.  The  latter,  when  produced  in  excess,  quickly  manifests 
its  power,  which,  under  normal  conditions,  is  concealed  by  the 
narcotic  poison. 

How  is  it  that  these  substances,  which  render  the  urine 
poisonous,  do  not  poison  the  patient?  Precisely  because  the 
urine  is  poisonous, — i.e.,  because  it  carries  off  the  poison.  But 


POISONS    ARE   ELIMINATED  BY   THE   URINE.  241 

if  the  kidneys  begin  to  work  defectively,  complications  appear — 
convulsions,  the  final  ataxo-adynamic  phenomena  of  every  dis- 
ease— which  may  result  not  only  in  secondary  nephritis,  but  also 
in  an  insufficiency  of  urine  during  the  death-agony.  The  death- 
struggle  is  a  form  of  poisoning,  as  all  the  signs  observed  in  the 
dying  testify,  from  the  pupillary  contraction  which  appears  at 
first  to  the  final  convulsion  and  the  last  throe. 


LECTURE   XXVII. 

PYOCYANIC  DISEASE.     POISONING  ACCIDENTS  IN  DIABETES. 

Do  pathological  poisons  really  exist  ?    Pyocyanic  disease.      The  researches  of 

M.  Charrin. Can  sugar  become  a  poisoning  agent  in  diabetic  subjects? 

Dehydration  is  the  cause  of  nearly  all  the  accidents  of  diabetes.     Aceto- 
naemia.    Diabetic  coma. 

HAVING  been  led  by  theory  to  seek  for  one  poisonous  substance 
in  disease,  I  have  found,  in  the  organism  of  patients,  substances 
which  may  be  poisonous,  but  they  occur  in  such  proportions  that 
it  is  impossible  to  attribute  the  poisoning  to  them  under  ordinary 
conditions.  Seeking  for  a  morbid  poison  I  have  only  been  able 
to  find  the  normal  one. 

In  pyretic  diseases,  or  those  of  a  rapidly -consumptive  nature, 
I  have  found  that  the  coloring  matter  produced  in  excess,  and 
potass,  liberated  by  the  too  rapid  destruction  of  cells,  both  having 
Convulsing  properties,  may  cause  poisoning  if  the  kidney 
become  impermeable,  whether  it  is  attacked  with  nephritis  or 
whether  its  action  is  suspended  as  in  febrile  or  agonic  oliguria. 
During  the  last  phases  of  disease,  we  may  observe  the  appear- 
ance of  the  signs  of  poisoning  that  are  characteristic  of  coloring 
matter  and  potass. 

Under  these  circumstances  the  poisoning  has  certainly  been 
prepared  indirectly  by  the  disease,  but  there  has  been  no  special 
poison  fabricated  by  it.  The  fact  of  knowing  that  the  lungs  no 
longer  act,  or  that  the  temperature  is  too  high,  when  we  see 
ataxo-adynamic  accidents  set  in,  does  not  give  us  the  right  to 
speak  of  pneumonic  poison,  tetanic  poison,  and  so  on.  We  see 
simply  a  phase  of  uraemic  poisoning,  with  this  distinction,  that 
the  poisoning  is  produced  by  exaggerated  disassimilation,  and 
that  it  is  retained  in  the  blood  through  the  inadequate  action  of 
the  kiclne37s.> 

This  does  not  mean  that  there  are  not  in  certain  maladies 
true  morbid  poisons,  engendered  by  the  normal  life  of  microbes 
or  the  diseased  life  of  human  cells.     But  the  difficulty  is  to 
collect  and  isolate  these  poisons. 
(242) 


BLUE  PUS.  243 

If  this  subject  could  be  studied  like  the  pathogenic  agent 
of  blue  pus,  it  could  perhaps  be  more  easily  explained.  Blue 
pus  is  characterized  by  two  things, — a  body  having  the  chemical 
characteristics  of  the  alkaloids,  and  which  has  long  been  recog- 
nized, viz.,  pyocyanine ;  and  a  microbe,  a  mobile  bacillus,  which 
produces  this  substance,  and  which  is  mentioned  by  Gessard. 
The  microbe  is  easily  recognized,  since  the  blue  color  of  the  sub- 
stance that  it  fabricates  betrays  it  wherever  it  is  met  with.  The 
blue  is  completely  fixed  by  chloroform ;  afterward,  in  the  pres- 
ence of  acidulated  water,  the  chloroform  is  discolored  and  the 
water  takes  a  roseate  tinge.  By  this  reaction  we  can  always 
recognize  this  organism,  which  develops  rapidly  and  resists  the 
action  of  all  the  other  ferments. 

Taking  advantage  of  this  characteristic,  M.  Charrin  has  made 
experiments  in  inoculation  and  injection  with  liquid  cultures. 
Clinical  surgery  has  shown  that  blue  pus,  when  brought  into 
contact  with  a  wound,  does  not  produce  infectious  accidents  ; 
but,  it  may  be  asked,  what  would  happen  if  it  forced  its  way 
through  the  barrier  of  the  tissues?  This  hypothesis  has  been 
answered  by  the  injection  into  the  veins  of  pure  "culture 
liquids"  containing  both  the  microbe  and  pyoc3'anine.  The 
subcutaneous  injection  seems  harmless,  hut  an  animal  that  is 
subjected  to  an  intra-venous  injection  of  1  or  2  cubic  centimetres 
of  liquid,  prepared  in  this  way,  becomes  feverish  and  tvuses  to 
eat ;  it  may  be  attacked  with  intense  albuminuria  and  diarrhoea  ; 
it  becomes  emaciated  and  ill.  We  must  mention  that  a  certain 
number  of  rabbits  prove  refractory,  and  that  often  considerable 
doses  are  required  in  order  to  succeed.  Is  this  malady  of  an 
infectious  nature?  We  know  that  microbes  are  cliininatnl 
by  the  urine  and  faecal  matter.  But  are  they  still  alive? 
Yes ;  since  we  observe,  simultaneously  with  their  presence,  the 
reaction  of  pyocyanine  in  the  liquids  impregnated  with  these 
substances. 

We  may  push  the  question  still  further,  and,  by  treating  the 
bacillus  and  the  chemical  substance  separately,  we  may  endeavor 
to  ascertain  their  respective  roles  in  the  mechanism  of  the  dis- 
ease. We  withdraw  the  microbes  from  the  liquids  in  which 
they  have  been  cultivated,  employing  for  this  purpose  either 


244  LECTURES  ON   AUTO-INTOXICATION. 

heat  and  filtration  or  filtration  by  means  of  the  tested  Chamber- 
land  cylinders;  *  we  find  in  the  filtered  liquids  all  the  reactions  of 
pyocyanine,  and  we  can,  moreover,  make  sure  by  cultivation  that 
these  liquids  no  longer  contain  any  microbes.  If,  under  these 
conditions,  we  inject  into  the  veins  of  a  rabbit  the  filtered 
liquid,  which  is  rich  in  pyocyanine,  we  find  that  the  toxicity  of 
this  liquid  is  comparatively  slight,  whether  we  inject  successive 
quantities  for  several  days,  or  whether  we  inject  at  once  60 
cubic  centimetres  of  the  liquid.  The  animals,  upon  receiving 
these  injections,  which  are  made  antiseptically,  show  only  transi- 
tory effects,  and  in  some  cases  can  be  cured  ;  whereas,  when  the 
same  liquids,  containing  microbes,  are  injected  in  the  same 
animals,  these  animals,  as  I  have  said,  become  diseased  and 
generally  die.  We  are  thus  led  to  think  that  in  the  development 
of  this  experimental  disease,  while  taking  into  account  the  action 
of  the  chemical  substance,  we  must  also  consider  the  material 
lesions,  nephritis,  enteritis,  etc.,  which  seem  to  be  created  by 
the  microbe  itself.  To  speak  of  nephritis  only,  for  instance,  we 
do  not  always  produce  it  in  a  lasting  form,  by  injecting  into 
a  rabbit,  in  a  certain  quantity,  crystallized  pj-ocyanine,  or  a 
liquid  containing  pyocyanine  deprived  of  microbes ;  whereas, 
when  we  inject  a  liquid  culture  containing  microbes,  if  the  animal 
survive  a  certain  number  of  days,  nephritis  is  established  perma- 
nently, and  microbes  are  found  in  the  blood,  the  kidneys,  and 
the  urine.  "Under  these  conditions  the  blood,  the  kidneys,  or  the 
urine,  on  being  treated,  show  the  presence  of  pyocyanine.  It 
is,  therefore,  from  these  experiments,  probable  that  the  microbe, 
besides  its  possible  chemical  action,  produces  a  traumatic  effect 
on  the  kidneys  and  causes  a  nephritis,  which  then  acts  on  its 
own  account,  and  places  the  animal  in  the  position  of  a  patient 
attacked  with  Bright's  disease,  f 

*  See  Wilson's  Hygiene,  page  232. 

t  The  results  indicated  were  obtained  by  experiments  on  the  rabbit ;  we  are  not 
speaking  of  those  that  can  be  obtained  upon  other  animals,— the  guinea-pig,  for 
instance,— and  by  varying  the  modes  of  introduction.  The  results  in  these  cases 
may  be  different,  and  this  is  not  surprising,  since  the  conditions  of  the  experiment 
are  changed.  M.  Charrin  is  of  opinion  that  fresh  reservations  should  be  made  as 
regards  the  role  of  the  chemical  substance.  Recent  experiments  have  shown  him 
that  the  pyocyanine  bacillus  could  live  under  certain  conditions  without  gener- 
ating pyocyanine  itself.  It  is,  therefore,  possible  that  in  the  animal  a  body  is  formed 
which  is  more  or  less  like  pyocyaiiine,  but  possesses  a  different  degree  of  toxicity 
and  acts  differently. 


CONSEQUENCES   OF    EXCESS   OF   SUGAR   IN    THE   BLOOD.  245 

We  must  now  endeavor  to  find  out  whether  the  poisons  are 
produced  in  consequence  of  a  disordered  state  of  the  general 
nutrition. 

As  regards  sugar,  the  formation  of  which  is  considered  by 
certain  physicians  as  the  result  of  a  disordered  state  of  nutrition 
of  the  liver,  can  we  look  upon  it  as  a  poison  ?  Not  in  my  opinion. 
Sugar  is  not  essentially  poisonous  ;  it  only  becomes  injurious  by 
its  quantity.  If  it  is  not  consumed,  transformed,  or  destroyed 
by  the  organs,  it  becomes  a  poison  like  carbonate  of  soda,  which, 
in  excess,  may  become  poisonous  although  it  forms  an  integral 
part  of  the  blood.  As  long  as  the  blood  contains  only  one  in  a 
thousand  of  sugar,  the  system  is  not  appreciably  affected ;  but 
above  3  per  1000  (Bernard)  or  5  per  1000  (Pavy)  the  effects 
of  poisoning  ensue,  and  a  special  pathological  condition  is 
established. 

One  of  the  first  symptoms  of  excess  of  sugar  in  the  blood  is 
glycosuria,  which  does  not  exist  when  there  is  only  1  per  1000 
of  sugar  in  the  blood.  When  this  proportion  is  increased,  the 
hyperglycaemia  deranges  the  quantity  of  the  urine.  In  fact, 
when  sugar  is  eliminated,  it  carries  awa}^  its  equivalent  of 
water  of  diffusion,  which  is  in  the  proportion  of  7  parts  of 
water  to  1  of  sugar.  Under  normal  conditions,  the  blood  does 
not  allow  itself  to  be  dehydrated ;  when  it  gives  up  a  portion 
of  its  water,  it  recovers  it  immediately  by  drawing  it  from 
the  plasmas  and  the  elements  of  the  tissues.  The  blood  cannot 
have  less  than  its  normal  percentage  of  water;  in  order  to 
supply  the  renal  secretion,  it  must  be  incessantly  receiving 
water,  which  is  either  conveyed  to  it  by  drinking,  or  which  it 
draws  from  the  tissues  and  especially  from  the  plasmas,  which 
represent  in  weight  a  third  of  the  economy.  If  the  water 
obtained  by  drinking  and  the  water  from  the  plasmas  fail  to 
keep  up  the  required  supply,  under  any  other  circumstances  than 
the  case  of  hyperglycoemia  the  renal  secretion  could  be  dimin- 
ished or  suppressed.  But  as  long  as  there  is  in  the  blood  water 
and  sugar  in  excess,  there  is  produced  a  glycosuria  accompanied 
by  the  water  of  diffusion  due  to  the  sugar;  when  the  glycaemia 
is  intense,  the  sugar,  which  must  necessarily  be  supplied  with 
its  equivalent  of  water  of  diffusion,  dehydrates  more  and  more 


246  LECTURES  ON   AUTO-INTOXICATION. 

the  plasmas  and  the  tissues.  One  of  the  primary  effects  of  poison- 
ing by  sugar  is,  therefore,  the  extraction  of  water  from  the  system. 
Then  a  modification  is  produced  in  the  phenomena  of  osmosis ; 
the  sugar,  having  rendered  the  blood  more  dense,  becomes  a  fresh 
medium  for  the  elements  of  the  system,  and  is  thus  another  cause 
of  the  abstraction  of  water  from  the  plasmas.  We  find  the  sensa- 
tion of  thirst  appear.  A  diminution  ensues  in  the  aptitude  of 
the  water  to  leave  the  blood  ;  the ,  pulmonary  exhalation  dimin- 
ishes as  well  as  the  cutaneous  exhalation. 

Under  normal  conditions  one-third  of  the  total  quantit}^  of 
water  that  passes  out  of  the  system  is  eliminated  by  the  lungs 
and  the  skin.  In  a  diabetic  subject,  according  to  Burger,  these 
emunctories  only  eliminate  one-twelfth. 

Among  the  consequences  of  this  dehydration  of  the  tissues, 
we  must  note  diabetic  cataract,  which  has  been  demonstrated 
by  an  ingenious  experiment  performed  by  M.  Lecorche.  This  is 
the  explanation  that  is  generally  admitted ;  but  in  reality  the 
crystalline  opacity  which  is  produced  experimentally  by  de- 
hydrating the  body  by  means  of  sugar  or  salt  is  not  cataract ; 
it  disappears  when  the  tissues  have  regained  their  normal  per- 
centage of  water.  Diabetic  cataract,  on  the  contrary,  is  per- 
manent, and  we  not  infrequently  see  it  developed  in  patients 
that  are  suffering  from  oedema,  in  which  case  there  is  no  question 
of  dehydration. 

As  the  results  of  the  derangemeut  of  the  nutritive  processes, 
we  note  the  appearance  of  anomalous  products  of  disassimilation, 
anomalous  albumens,  so  frequent  in  diabetic  subjects,  and  the 
increase  of  extractives  or  urea ;  these  features  are  not  the 
unfailing  rule,  but  they  are  accidents  that  might  be  explained 
by  hyperglycsemia. 

The  dehydration  of  the  tissues,  when  it  exists  onty  in  a  mod- 
erate degree,  provokes  certain  functional  disturbances,  which,  in 
the  nerve-elements,  take  the  form  of  an  exaggerated  excitability 
and  rapid  fatigue,  and,  in  the  muscular  elements,  are  manifested 
by  cramp,  as  in  cholera.  A  higher  degree  of  dehydration  is 
attended  by  nervous  accidents  of  great  gravity,  in  which  cate- 
gory we  may  perhaps  include  diabetic  coma. 

When  we  were  discussing  typhoid  fever  and  dyspepsias,  we 


COLOR-TEST   OP   URINE    IN    ACETON^EMtA.  247 

mentioned  a  particular  alteration  of  the  fluids,  in  consequence 
of  which  the  breath  exhales  an  odor  similar  to  that  of  chloroform 
or  rennet-apples,  and  also  a  particular  chemical  reaction  of  the 
urine.  It  has  been  suggested  that  this  odor  of  the  breath  and 
this  reaction  of  the  urine  may  belong  to  acetone. 

In  certain  urines  a  few  drops  of  perchloride  of  iron  will  give 
a  claret-colored  tint,  or  the  shade  produced  may  be  darker,  even 
violet.  The  reddish-brown  tinge  is  very  frequent  under  various 
morbid  conditions;  this  is  due  to  substances  the  nature  of  which 
has  not  been  chemically  defined  ;  acetone  gives  a  wine-red  color, 
but  this  tint  may  be  produced  by  other  substances.  This 
reaction  is  met  with  in  certain  forms  of  dyspepsia,  in  t3'phoid 
fever,  scarlatina,  leucocythaeinia,  and  in  pernicious  ancemia  ;  it  is 
very  frequent  in  diabetes.  Nevertheless,  in  many  diabetic  sub- 
jects, we  may  observe  for  years  the  chloroform ic  odor  of  the 
breath,  without  ever  detecting  it  in  the  urine,  and  still  rarer 
in  this  disease  is  the  reaction  of  perchloride  of  iron.  If  a  salt 
due  to  the  combination  of  diacetic  ethyl  with  soda  resulted  from 
the  transformation  of  the  acetone,  we  should  obtain  the  colora- 
tion without  the  odor ;  otherwise  we  get  the  chloroformic  odor 
in  the  urine  without  the  coloration.  In  short,  in  nearly  all 
cases  of  diabetic  coma,  perhaps  in  all,  we  find  the  color-reaction 
of  the  urine  and  the  odor  of  the  breath.  It  is  therefore  proba- 
ble that  in  these  cases  poisoning  exists  similar  to  that  of 
severe  dyspepsia.  I  know  nothing  of  the  pathogenic  condi- 
tions of  those  forms  of  poisoning  termed  acetonaemic.  The 
clinical  fact  having  been  observed  by  Brieger,  at  the  clinic  of 
Frerichs,  under  various  pathological  conditions ;  by  Senator,  by 
Jaksch  in  carcinoma  of  the  stomach  and  in  severe  forms  of  dys- 
pepsia, and  by  myself  in  typhoid  fever  and  in  a  very  great  num- 
ber of  cases  of  dilatation  of  the  stomach,  it  seems  to  me  pr« •! ta- 
ble that  the  cause  of  it  is  some  morbid  substance  elaborated  in 
the  intestines.  These  accidents  can  be  reproduced  in  every 
feature  experimentally,  as  has  been  shown  l>y  tin-  experiments  of 
M.  de  Gennes. 

However  this  may  be,  we  note  in  certain  diseases,  not  neces- 
sarily infectious,  a  body,  or  a  series  of  bodies,  which,  on  being 
eliminated  by  the  urine,  give  a  red  coloration  upon  the  addition 


248  LECTURES  ON   AUTO-INTOXICATION. 

of  perchloride  of  iron.  These  bodies  are  the  result  of  the  defec- 
tive elaboration  of  matter  by  the  human  organism ;  they  are 
anomalous  substances,  not  engendered  by  microbes.  Amongst 
these  substances  are  acetone,  diacetic  ether,  and  oxybutyric 
acid,  which  are  poisonous ;  thus  we  find  in  this  class  some  true 
morbid  poisons.  In  diabetes  this  reaction  of  the  urine  and  the 
odor  of  the  breath  may  serve  as  a  basis  of  diagnostic  and  prog- 
nostic indication. 

Two  years  ago  the  odor  of  the  breath  enabled  me  to  form 
the  diagnosis  in  a  case  in  which  a  child  had  been  suddenly 
attacked  with  comatose  symptoms.  It  was  not  known  that  the 
child  was  ill  when  he  was  brought  home  from  school  in  a  state 
of  complete  coma.  The  skin  was  dry,  and  there  was  no  patellar 
tendon  reflex.  Guided  by  the  odor  of  the  breath  and  the 
absence  of  the  reflex,  I  expected  to  find  sugar  in  the  urine ;  but, 
as  the  child  passed  no  urine,  I  had  those  parts  of  his  clothing 
washed  that  were  likely  to  be  stained  with  urine  ;  in  the  infusion 
thus  procured  I  obtained  the  reaction  of  sugar,  and  was  thus 
enabled  to  pronounce  the  attack  to  be  diabetic  coma,  which 
ended  in  death  in  a  few  hours. 


LECTURE  XXVIII. 

POISONING  BY  PATHOLOGICAL  POISONS.     CHOLERA. 

Former  opinions  as  to  the  causes  and  the  nature  of  cholera.  Influence  of  the 
prevailing  pathogenic  theories  on  the  choice  of  prophylactic  modes  of 
treatment.  Mode  of  propagation  of  cholera.  Importance  of  the  transmis- 
sion by  water.  Other  possible  modes  of  contagion.  Attempts  to  discover 
the  agent  of  infection.  The  French  Commission  in  Egypt.  The  researches 
and  opinions  of  Koch.  The  value  of  the  comma  bacillus.  Studies  of  the 
trausmissibility  of  cholera  to  animals. 

IN  studying  diseases  caused  by  poisoning  I  am  naturally  led 
to  speak  of  cholera  and  to  sum  up  the  knowledge  that  we  pos- 
sess of  its  nature.  All  that  has  been  said  with  regard  to  the 
etiology  of  the  plagues  of  antiquity  and  of  the  Middle  Ages  has 
been  repeated  in  modern  times  with  regard  to  cholera.  It  was 
at  first  attributed  to  the  wickedness  of  man  and  the  anger  of 
God;  to  this  religious  view  succeeded  the  idea  of  poisoning  by 
means  of  witchcraft,  a  theory  to  which  were  attached  corollaries 
of  certain  practices  that  were  reputed  to  be  prophylactic.  Wells 
and  springs  were  believed  to  be  poisoned.  Certain  persons,  and 
especially  doctors,  were  accused  of  being  the  promoters  of  direct 
poisoning.  These  absurd  accusations  were  made  in  Paris  in  1832 
and  in  Naples  in  1884.  In  the  past,  Jews  and  doctors  were  often 
associated  together  in  public  denunciations  relating  to  pestilen- 
tial diseases.  They  were  suspected  of  poisoning  food.  Travel- 
ers generally  were  also  suspected, — not  only  those  who  were 
infected,  but  all  foreigners;  a  foreigner  was  looked  upon  as  a 
deadly  enemy.  Previous  to  the  pestilence  being  attributed  to 
water,  the  air  and  the  clouds  had  been  made  responsible  for  it ; 
there  was  a  time  when  a  certain  cloud  hovering  over  a  town  was 
reputed  to  be  pestilential  in  virtue  of  some  peculiar  reflection  or 
some  unusual  tint.  These  ideas  were  prevalent  in  the  fourteenth 
and  fifteenth  centuries,  and  we  have  actually  seen  them  revived  in 
the  second  half  of  the  nineteenth  century !  Naturally  the  pro- 
phylactic measures  proposed  were  in  harmon}'  with  these  etiolog- 
ical  chimeras.  It  was  necessary  to  avert  the  divine  wrath  by 

(249) 


250  LECTURES   ON   AUTO-INTOXICATION. 

expiatory  deeds,  by  penances  and  fastings  imposed  on  evil-doers. 
Believers  in  the  efficacy  of  pilgrimages  and  processions  are  to  be 
found,  even  at  the  present  day,  in  all  classes  of  society. 

People  were  more  practical  during  the  Black  Plague ;  they 
appointed  sentinels  to  guard  the  wells.  In  Paris  also,  in  1865 
and  in  1873, 1  noticed  that  the  casks  of  the  water-carriers  on  the 
Quai  St.  Bernard  were  guarded  by  the  police.  Was  this  a  con- 
cession to  popular  prejudices  on  the  part  of  the  authorities,  or 
did  the  authorities  share  these  prejudices?  Sentinels  were  also 
placed  at  the  gates  of  towns,  the  portcullis  was  lowered  and  the 
drawbridge  raised.  In  our  own  times  sanitary  cordons  have  been 
drawn  up  round  uninfected  towns  in  the  south  and  travelers 
have  been  received  with  gunshot. 

Yet- a  calm  examination  of  facts  has  shown  that  cholera  is  a 
disease  that  is  endemic  in  certain  countries ;  for  centuries  it  has 
been  prevalent  on  the  Delta  of  the  Ganges.  Thence  it  spreads ; 
it  follows  a  caravan  and  marks  the  route  from  the  Ganges  to 
Mecca,  where  it  attacks  the  Mussulmans,  Hindoos,  etc.,  assembled 
together;  on  its  return  it  rages  amongst  all  the  caravans,  some- 
times completely  destroying  them,  or  it  advances  with  them  as 
far  as  Hedjaz  and  Persia  ;  it  then  continues  its  migration  through 
Russia  to  Western  Europe.  Its  progress  has  also  been  traced 
from  Hedjaz  into  Egypt,  to  Alexandria,  where  it  forms  a  fresh 
centre,  thus  menacing  Europe  from  two  sides.  We  know  that  its 
migrations  are  determined  by  commerce  and  by  routes  followed 
by  the  great  human  currents, — seas,  rivers,  roads,  and  railways. 

What  strikes  us  in  the  history  of  cholera,  when  we  hear  of 
its  having  appeared  almost  simultaneously  at  several  points,  is 
that  it  is  always  a  sea-coast  town  that  is  first  attacked.  It  never 
appears  first  in  an  inland  district. 

With  regard  to  this,  it  has  been  asserted  that,  in  a  certain 
number  of  instances,  a  port  has  been  infected  without  any  patient 
suffering  from  cholera  having  disembarked  there.  But  even  if 
the  infection  is  not  conveyed  by  those  who  have  been  attacked, 
the  ship  itself  has  been  contaminated  or  brings  infected  linen. 
The  corpses  of  those  that  have  succumbed  to  the  disease  may 
have  been  thrown  into  the  sea,  but  the  discharges  and  the  linen 
impregnated  with  them  have  remained  on  board.  In  these  cases 


DISSEMINATION   OP  CHOLERA.  251 

the  linen  has  never  been  disinfected;  the  truth  has  not  been 
told  as  regards  this  matter.  We  can  see  how  much  importance 
may  be  attached  to  the  official  statements  relating  to  the  disin- 
fection of  suspected  ships  or  cargoes  by  the  pretense  of  disinfec- 
tion that  we  witnessed  during  the  last  epidemic.  The  authorities 
did  right  not  to  insist  upon  the  disinfection  of  the  people  them- 
selves ;  I  am  not  so  sure  that  they  were  justified  in  not  ordering 
the  thorough  disinfection  of  clothes,  linen,  and  bedding  after 
landing ;  it  was  then  too  late.  But  at  the  lazaretto  how  did 
they  act?  They  did  not  even  demand  that  the  people  entering 
the  lazaretto  should  take  a  bath. 

Since  that  time  a  great  outcry  has  been  raised  against  us  by 
the  public  and  the  press,  and  public  authorities  have  been  shaken 
in  the  confidence  they  had  placed  in  doctors,  and  begun  to  ask 
themselves  whether  the  latter  had  ever  deserved  this  confidence. 

Often  still,  when  we  follow  the  dissemination  of  cholera 
through  France,  we  can  trace  it  to  linen  that  has  not  been  disin- 
fected. On  studying  the  history  of  a  great  number  of  local  epi- 
demics, we  find  that  laundresses  have  been  attacked  first.  The 
dissemination  of  cholera  has  also  been  attributed  to  water.  It 
is  probable  that  several  centres  have  been  created  by  this  agency. 
It  is  almost  an  established  fact  that,  in  towns,  the  districts  that 
have  escaped  have  been  those  which  could  not  come  into  contact 
with  the  discharges  of  those  attacked,  conveyed  through  the 
medium  of  water;  on  the  other  hand,  our  canal  of  the  Ourcq, 
with  its  array  of  boats,  was  one  of  the  most  powerful  agents  of 
transmission — at  an}^  rate,  in  the  last  epidemic ;  and  the  districts 
first  attacked  were  a  part  of  the  Faubourg  Saint  Antoine  and  the 
Rue  Sainte-Marguerite, — those  to  which  the  water  of  the  Ourcq 
was  brought  by  direct  canalization. 

In  hospitals  where  water  is  economized,  where  infected  and 
nnfiltered  water  might  be  used  for  culinary  nnd  i>li:inu:iriMitir:il 
purposes,— at  La  Charite*  and  at  Lariboisiere, — cases  occurred* 
within  the  building  before  any  cholera  patient  from  the  town 
had  been  brought  to  the  hospital.  To  the  same  cause  mny  IT 
attributed  the  disastrous  infection  of  the  Asylum  for  Old  People, 
in  the  Rue  de  Bretenil.  As  regards  the  other  centres  of  infection, 
it  is  impossible  to  explain  their  origin  categorically,  on  account 


252  LECTURES  ON   AUTO-INTOXICATION. 

of  the  mixing  of  the  water  of  the  Dhuys  and  the  Vanne  with 
that  of  the  Ourcq,  in  consequence  of  the  anastomoses  which  are 
the  great  fault  of  our  system  of  canalization,  and  which  cause  an 
ebb  and  flow  from  one  stream  to  the  other. 

With  regard  to  the  spreading  of  infection  by  water  we  cannot 
believe  that  there  is  any  truth  in  the  assertion  that  the  infection 
may  be  conveyed  up  the  river,  along  the  Rhone  for  instance, 
from  Marseilles  to  Avignon  ;  no  one,  on  reflection,  can  admit 
that  the  germs  could  be  carried  against  the  stream. 

The  link  that  is  missing  in  the  chain  of  evidence  of  contagion 
is  direct  contagion.  But  if  measles,  small-pox,  and  scarlatina 
are  spread  chiefly  in  this  way,  we  can  understand  that  with  typhoid 
fever  and  cholera  the  infection  is  conveyed  not  through  the 
body  itself,  but  through  what  comes  from  the  body.  We  must 
also  take  into  account  the  vegetables  that  grow  close  to  the  earth 
and  that  are  eaten  raw,  and  various  modes  of  contamination  by 
drinking.  We  have  naturally  been  led  to  consider  cholera  as  a 
disease  that  is  indirect^  contagious,  like  typhoid  fever  ;  it  was 
natural,  therefore,  to  look  for  the  agent  of  contagion  in  cholera. 
The  pathogenic  study  must  be  entered  upon  from  a  parasitic 
point  of  view,  and,  in  fact,  the  first  reports  of  the  discovery  of 
organisms  said  to  be  infectious  date  from  1848.  These  first 
reports  have  no  scientific  value,  but  they  serve  to  show  the  spirit 
in  which  the  investigations  have  been  carried  on  since  that  time. 

Virchow  in  1848  and  Hallier  in  1867  found  frequently  para- 
sitic organisms,  but  in  liquids  where  microbes  constantly  exist. 
Regular,  systematic  investigations  did  not  commence  until  the 
European  commissions  were  sent  to  Alexandria,  in  1883;  these 
researches  were  instituted  by  the  French  Commission,  which  in- 
cluded among  its  members  Messrs.  Straus,  Roux,  Nocard,  and 
Thuillier,  and  by  the  German  Commission  of  R.  Koch.  The 
great  secrecy  observed  by  the  French  Commission  was  fully  justi- 
fied. At  first,  it  is  true,  the  telegraph  told  too  much  ;  but  when 
the  members  of  the  Commission  spoke  themselves,  they  expressed 
their  doubts  at  the  right  time.  They  had  found  traces  of  an 
organism  in  the  blood,  but  they  added  that  this  differed  singu- 
larly from  the  various  ferments  known,  not  being  colored  by  the 
ordinary  processes  and  not  being  susceptible  of  cultivation. 


CHOLERA   AND   THE   COMMA   BACILLUS.  253 

Koch  has  also,  on  the  other  hand,  discovered  an  organism  in 
the  form  of  a  comma,  which  cannot  be  classed  under  any  of  the 
five  groups  of  ordinary  parasitic  intestinal  microbes.  These 
comma-shaped  organisms  appeared  to  him  to  be  on  the  surface 
or  in  the  interior  of  the  intestine  of  cholera  patients,  and  they 
are  sometimes  in  such  quantities  as  to  constitute  nearly  the 
whole  of  the  excretions.  Koch  has  seen  them  in  the  choleraic 
discharges,  on  the  cells  whilst  desquamation  is  going  on,  or 
between  them  and  penetrating  into  the  interior  of  the  intestinal 
glands  and  into  the  superficial  parts  of  the  mucous  membrane ; 
but  he  has  neve*  found  them  anywhere  else,  having  searched  for 
them  vainty  in  the  ganglia,  the  kidne3's,  the  spleen,  the  blood, 
and  the  lymph,  and  yet  he  has  already  asserted  that  these  organ- 
isms' are  the  pathogenic  agents.  The  comma  bacillus  is  a  short, 
slender,  moving  body,  which  fixes  certain  stains  like  other  patho- 
genic organisms.  The  examination  of  this  germ  presents  no 
difficulty.  It  is  slightly  curved  ;  its  dimensions  are  as  follow  : 
length,  from  1^/K  to  2|^;  breadth,  from  0.6ft  to  0.7/M.  These 
comma  microbes  maybe  found  linked  together  by  twos  or  threes, 
so  as  to  form  a  little  chain  ;  they  may  be  curved  in  opposite  di- 
rections or  in  the  same  direction,  so  as  to  appear  in  the  form  of 
an  S,  or  of  part  of  a  circle,  or  they  may  assume  a  spirillar  form. 
Such  is  the  statement  of  Koch,  which  rests  solely  on  the  empiri- 
cal fact  of  his  having  found,  on  the  surface  of  the  intestine,  an 
organism  which  is  not  present  under  ordinary  conditions,  and 
which  is  very  abundant  in  cholera.  But  it  has  yet  to  be  ex- 
plained how  this  organism  causes  the  disease.  Koch  says  that, 
after  it  has  left  the  intestine,  he  can  continue  its  germination 
on  any  moist  surface,  on  the  surface  of  food,  and  on  the  soil 
when  the  temperature  is  not  too  low  and  when  the  atmosphere 
is  damp.  The  question  then  arises  as  to  how  a  district  is  ever 
freed  from  it.  The  fact  that  a  lake  contained  any  of  these  organ- 
isms would  be  sufficient  to  render  it  permanently  infected,  and 
Koch  actually  discovered  in  India  a  lake  the  waters  of  which 
contained  these  comma  bacilli,  which  he  was  able  to  cultivate; 
in  this  way  there  would  be  a  perpetual  interchange  of  infectious 
germs  between  the  earth  and  man.  This  explanation  is  simple ; 
in  fact,  it  is  too  simple  to  be  admitted.  If  it  were  true,  how  is 


254  LECTURES   ON    AUTO-INTOXICATION. 

it  that  in  Paris  and  in  Germany,  where  the  cultivation  of  chol- 
era germs  has  been  studied  unceasingly,  the  various  labora- 
tories have  not  been  infected?  How  is  it  that  the  disease  has 
not  broken  out  amongst  the  experimentalists  ? 

In  order  to  distinguish  the  bacillus  which  he  has  found  in 
those  attacked  with  cholera,  Koch  has  endeavored  to  find  cer- 
tain special  characteristics — a  different  action  on  gelatin,  and  a 
particular  configuration  in  the  zone  of  liquefaction — which 
would  reveal  the  nature  of  the  bacillus.  This  characteristic, 
however,  is  not  wholly  convincing. 

It  must  be  remarked  that  the  same  organism  has  been  found 
in  cases  of  sporadic  cholera  by  Finckler,  of  Bonn  ;  it  was,  per- 
haps, somewhat  larger  than  Koch's  bacillus.  Thus,  in  two  dis- 
eases which  resemble  each  other  in  their  symptoms  to  such  a 
degree  that  the  most  learned  physicians  do  not  express  a  decided 
opinion  as  to  the  nature  of  the  accidents  attendant  upon  them 
until  after  the  extension  and  propagation  of  the  disease,  we 
find  microbes  exactly  similar  in  form.  Against  the  pathogenic 
value  to  be  attached  to  the  comma  microbes  it  has  been  urged 
that,  as  they  exist  only  in  the  intestine,  they  could  not  so 
rapidly  cause  such  serious  general  disorders.  But  it  may  be 
that  these  organisms  engender  a  toxic  substance,  which,  when 
once  absorbed,  affects  all  the  cells  of  the  sj-stem. 

Other  investigators — M.  Emmerich  at  Vienna,  and  M.  Doyen 
here — think,  moreover,  that  they  have  found  pathogenic  mi- 
crobes in  some  of  the  viscera.  M.  Emmerich,  who  states  that 
he  has  seen  them,  did  not  recognize  amongst  them  the  comma 
bacillus.  M.  Doyen,  not  having  absolutely  detected  them  in 
sections,  draws  conclusions  from  sterilized  cultures  made  with 
portions  of  the  liver  and  kidneys,  in  which  the  existence  of  the 
microbe  was  not  shown  by  the  microscope ;  these  cultures  had 
reproduced  the  comma  bacillus. 

All  this  consists  merely  of  hypothesis.  I  am  ready  to  grant 
that  the  comma  bacillus  may  be  a  microbe  that  is  peculiar  to 
cholera,  although  it  has  been  found  in  the  saliva  of  people  not 
suffering  from  that  disease.  But  what  conclusions  can  be  drawn 
from  the  discovery  of  this  microbe?  It  has  been  cultivated, 
but  these  cultivations  have  not  succeeded  in  reproducing  the 


FAILURE   TO   PRODUCE   CHOLERA   EXPERIMENTALLY.  255 

disease.  Is  it  likely  that  the  result,  which  could  not  be  obtained 
even  from  the  discharges  of  the  patients  themselves,  could  be 
obtained  from  the  supposed  agent  of  infection  of  cholera,  culti- 
vated and  isolated,  when  not  an  atom  of  the  organism  of  the 
person  attacked  with  the  disease  had  been  removed  with  it? 
Since  1865  and  1866  attempts  have  been  made  to  produce  cholera 
experimentally  with  the  perspiration,  the  vomit,  and  the  dis- 
charges of  cholera  patients.  The  experimentalists  have  suc- 
ceeded in  killing  animals,  probably  by  communicating  to  them 
certain  forms  of  septiceemia,  but  not  by  reproducing  cholera ;  and 
yet  the}'  hope  to  succeed  by  the  introduction  of  the  great-grand- 
nephews  of  microbes  that  have  been  taken  from  material  that 
will  not  of  itself  produce  cholera ! 

It  was  thought  that  the  failure  of  the  experiment  was  due 
to  a  defective  method  of  introducing  the  pathogenic  organisms 
into  the  intestine,  because  they  did  not  avert  the  protecting 
influence  of  the  gastric  juice,  the  acidity  of  which  would  pre- 
vent the  development  of  the  microbes.  Now,  since  1832,  it  has 
been  erroneously  asserted  that  the  choleraic  discharge  is  always 
neutral  or  alkaline  ;  I  have  found  it  to  be  acid.  The  acidity  of 
the  intestinal  liquid  was  slight,  but  was  still  present  at  the 
moment  of  death.  This  fact  contradicts  the  theory  of  the  sup- 
posed protective  influence  that  would  be  exercised  by  the  gastric 
juice.  Moreover,  if  animals  do  not  take  cholera  when  choleraic 
matter  is  introduced  into  their  stomachs,  how  is  it  that  the  dis- 
ease is  conveyed  through  the  gastric  channel  in  the  case  of  men, 
who  also  have  an  acid  gastric  juice  ?  Certainly  they  have  it  no 
longer  when  they  are  suffering  from  cholera,  but  they  had  it  up 
to  that  time. 

When  we  introduce  the  agents,  that  are  supposed  to  generate 
cholera,  directly  into  the  duodenum,  the  action  of  the  bile 
being  suppressed  by  means  of  a  ligature  round  the  bile-duct 
(Nicati  and  Rietsch),  accidents  are  produced  which  resemble 
those  of  cholera  ;  and  as  it  is  found,  at  the  post-mortem  exam- 
ination of  cholera  patients,  that  the  gall-bladder  is  distended, 
and  that  there  is  no  bile  in  the  intestine,  the  development  of 
cholera  in  man  is  attributed  to  the  suppression  of  the  biliary 
secretion.  Bat  it  is  because  the  patient  has  cholera  that  we 


256  LECTURES  ON   AUTO-INTOXICATION. 

find  in  him  the  biliary  secretion  suppressed.  After  examining 
all  the  theories  that  have  been  expressed  and  all  the  experiments 
that  have  been  made,  I  arrive  at  the  conclusion  that  the  proof 
of  the  transmissibility  of  cholera  to  animals  is  still  wanting ; 
they  have  been  caused  to  die  sometimes  from  peritonitis,  from 
septicaemia,  or  from  poisoning,  but  not  from  cholera. 


LECTURE  XXIX. 

CHOLERA  (CONTINUED). 

Objections  to  the  pathogenic  value  of  the  comma  bacillus.  Introduction  of  the 
microbe  by  the  hypodermic  method ;  M.  Ferran's  inoculations.  Experi- 
mental researches  relating  to  the  value  of  the  comma  bacillus.  Intestinal 
antiseptic  treatment  does  not  prevent  choleraic  accidents.  Search  after  a 
poison  in  the  discharges  of  cholera  patients,  in  their  tissues  and  their  secre- 
tions. The  intra-venous  injection  of  the  urine  of  cholera  patients  into  animals 
reproduces  most  of  the  symptoms  of  cholera. 

IN  the  critical  examination  which  I  have  made  of  the  pathog- 
eny  of  cholera  I  have  examined  the  claims  of  Koch's  bacillus, 
and  I  have  found  various  objections  calculated  to  lessen  the 
confidence  that  might  be  felt  with  regard  to  its  importance. 
The  only  argument  of  any  weight  in  favor  of  Koch's  opinion  is 
the  presence,  in  the  second  part  of  the  intestines  of  those  attacked 
with  cholera,  of  special  organisms  not  found  in  the  intestines  of 
healthy  people,  nor  in  those  of  patients  suffering  from  other  dis- 
eases ;  it  is,  in  fact,  the  presence  of  these  organisms  from  the 
very  commencement  of  the  choleraic  attacks,  often  in  consider- 
able  quantity  and  sometimes  to  the  exclusion  of  all  other 
microbes,  in  the  alimentary  canal.  With  the  exception  of  this 
empirical  fact,  which  only  leads  to  a  hypothesis,  all  the  argu- 
ments brought  forward  are  misleading. 

The  demonstration  to  be  desired  was  to  obtain  the  suspected 
organism  in  a  state  of  purity,  and  by  its  introduction  into  a 
healthy  body  to  reproduce  cholera.  It  was  thought  that  this 
experiment  could  only  be  tried  on  animals.  Now,  animals  do 
not  contract  this  disease.  They  have  always,  both  spontaneously 
and  experimentally,  resisted  the  influence  of  choleraic  discharges 
introduced  directly  into  their  bodies.  Could  it,  then,  be  expected 
that  cholera  would  be  communicated  to  them  by  means  of  the 
cultivated  germs?  It  seemed  highly  improbable;  but,  neverthe- 
less, attempts  have  been  made  to  realize  this  result  by  distorting 
nature,  so  to  speak. 

»  (257) 


258  LECTURES  ON   AUTO-INTOXICATION. 

Experimentalists  endeavored  to  get  rid  of  whatever  might 
protect  the  animal  against  the  action  of  the  cholera  germ,  viz., 
the  gastric  juice,  the  bile,  and  the  intestinal  movements.  They 
rendered  the  gastric  juice  alkaline,  they  conveyed  the  organism 
supposed  to  be  pathogenic  directly  into  the  duodenum,  and 
they  introduced  into  the  peritoneum  as  much  as  5  grammes  of 
tincture  of  opium  per  kilogramme  of  the  animal.  The  results 
obtained  were  various.  Sometimes  death  ensued,  but  more  often 
the  animal  survived.  When  death  occurred,  it  was  generally 
from  peritonitis  or  septicaemia.  No  results  calculated  to  con- 
vince us  of  the  truth  of  the  theory  were  obtained  ;  only  Messrs. 
Nicati,  Rietsch,  Koch,  Ferran,  and  Van  Ermengen  are  convinced. 
Others,  even  M.  Cornil,  who  still  holds  that  the  comma  bacillus 
is  really  the  cholera  bacillus,  make  formal  reservations  with 
regard  to  the  subject  of  the  experimental  reproduction  of 
cholera. 

These  results,  which  I  consider  negative,  do  not,  however, 
prove  that  Koch's  bacillus  is  not  pathogenic.  They  only  prove 
that  animals,  which  are,  as  we  know,  refractory  to  the  action  of 
choleraic  matter,  also  resist  the  cultivated  descendants  of  the 
microbes  which  it  contains.  But  is  it  the  same  with  man  ?  He 
contracts  cholera  spontaneously.  Is  he,  then,  attacked  with 
symptoms  of  cholera  when  the  comma  bacillus  is  developed  in 
his  system  ?  We  cannot  quote  any  experiment  of  importance  in 
answer  to  this  question.  We  may  mention  the  experiments  of 
Bochefontaine,  who  swallowed  pills  containing  choleraic  dis- 
charge :  he  experienced  nausea  and  even  vomiting.  He  inoc- 
ulated himself  in  the  cellular  tissue  with  the  liquid  in  which  the 
germs  were  cultivated :  inflammatory  swellings  resulted,  but 
there  was  no  sign  of  the  general  symptoms  of  cholera.  The  first 
experiment  must  not  be  considered  absolutely  convincing.  The 
bacilli  might  be  absent  from  the  matter  introduced  into  the 
system,  or  they  might  be  in  a  very  small  quantity,  or  the  mode 
of  administration  might  have  neutralized  them.  The  second 
method  cannot  be  appealed  to,  as  cholera  is  not  contracted  by 
hypodermic  inoculation.  All  that  we  know  goes  to  prove  that 
the  infectious  agent  is  introduced  through  the  digestive  channels. 

This  mode  of  inoculation  has  been  repeated  by  M.  Ferran. 


INOCULATION    OF   CHOLERA.      FERRAN.  259 

He  obtained  the  local  phenomena  experienced  by  Bochefontaine, 
— local  septic  action  in  the  tissues,  rarely  terminating  in  suppu- 
ration. I  do  not  know  what  value  may  be  attached  to  these 
inoculations  from  a  prophylactic  point  of  view.*  But  I  can  see 
already  objections  to  his  methods  of  procedure.  In  any  case,  as 
far  as  man  is  concerned,  the  facts  obtained  by  experiment  do 
not  enable  us  either  to  admit  or  deny  the  theories  of  Koch  with 
regard  to  his  bacillus ;  but,  experimental  proofs  being  wanting, 
observation  may,  in  a  roundabout  fashion,  lead  us  to  certain 
conclusions. 

Before  the  period  when  I  had  to  treat  cholera  patients  in  the 
last  epidemic  I  had  for  a  long  time  reflected  on  what  course  I 
should  adopt  if  cholera  did  break  out.  I  had  seen  that  the 
results  of  physiological  treatment  were  absolutely  nil,  with  the 
exception  of  intra-venous  injections.  On  the  other  hand,  I  knew 
the  uselessness  of  all  empirical  modes  of  treatment.  Opium, 
alcohol,  etc.,  have  given  the  same  statistical  results.  I  was  thus 
justified  in  making  an  experiment  in  pathogenic  therapeutics 
at  the  time  when  a  new  doctrine  gave  us  the  hope  of  defending 
the  patient  against  the  parasitic  germ  that  was  supposed  to 
menace  his  life. 

*  At  the  time  this  lecture  was  delivered  wo  had  no  definite  information  to  enable 
us  to  form  an  opinion  on  the  experiments  of  Ferran.  It  could  only  be  said  that  the 
principle  of  his  method,  if  there  was  any  principle  in  it,  had  not  been  proved  so  far 
as  cholera  was  concerned.  The  attempt  to  create  a  sort  of  immunity  from  a  disease 
by  simply  changing  the  mode  of  introduction  of  a  microbe  is  a  principle  that  was 
known  before  M.  Ferran's  time.  Messrs.  Arloing,  Cornevin,  and  Thomas  were  the 
first  to  demonstrate  it,  in  their  splendid  experiments  on  symptomatic  charbon.  But 
what  is  true  of  one  pathogenic  agent  of  disease  may  be  false  as  regards  another,  and 
we  should  therefore,  in  this  case  as  in  all  others,  guard  against  hasty  generalizations. 
Unfortunately,  the  importance  of  the  results  announced  by  M.  Ferran  is  considerably 
diminished  by  the  report  of  the  French  Commission,  composed  of  Messrs.  Brouardel, 
Charrin,  and  Albarran.  This  report  shows  us  that  M.  Ferran  was  not  able,  or,  at  all 
events,  not  willing,  to  give  proofs  of  what  he  had  advanced,  both  as  regards  the 
morphology  of  the  comma  bacillus  and  the  effects  obtained  from  it  upon  animals. 
The  phenomena  observed  in  persons  inoculated  in  no  way  resemble  those  of  a  slight 
attack  of  cholera,  as  the  Spanish  physician  asserted  ;  their  blood  never  contains  any 
of  the  bacilli.  Moreover,  M.  Ferran  refuses  to  explain  the  composition  and  prepara- 
tion of  his  lymph,  or,  if  he  gives  an  explanation,  he  abandons  it  a  few  days  after  for 
another.  Lastly,  the  statistics  that  ho  publishes,  although  numerous,  are  far  froa» 
being  unassailable.  In  short,  the  scientific  value  of  M.  Ferran's  method  has  not  yet 
been  proved.  This  is  the  verdict  pronounced  by  the  French  Commission,  and  we 
must  own  that  tins  verdict  has  boon  in  no  way  weakened  by  the  later  reports  of  the 
other  Commissions  (Belgian,  American,  Italian,  and  Spanish)  that  were  sont  to 
Valencia  for  the  same  purpose. 


260  LECTURES  ON    AUTO-INTOXICATION. 

Accepting,  therefore,  the  theory  of  Koch  provisionally, 
everything  seemed  to  indicate  that  antiseptic  treatment  adapted 
to  cholera  was  the  path  to  follow.  If  we  were  dealing  with  an 
agent  of  infection  that  was  scattered  through  the  blood  and  the 
tissues,  all  idea  of  antiseptic  treatment  would  have  had  to  be 
given  up.  But  we  had  before  us  a  doctrine  that  asserted,  authori- 
tatively, arguments  that  were  capable  of  misleading.  I  therefore 
applied  the  doctrine  of  Koch  to  the  therapeutics  of  cholera  in  all 
sincerity  and  good  faith.  It  may  be  summed  up  thus :  Cholera 
is  produced  by  a  poison  formed  by  organisms  in  the  intestinal 
canal;  it  is  an  infection  of  an  accessible  surface.  We  were 
able  to  destroy  by  antiseptics  other  microbes  in  the  alimentary 
canal.  Therefore,  if  Koch  was  right,  it  was  necessary  to  intro- 
duce into  the  alimentary  canal  a  substance  capable  of  destroying 
life  in  all  the  microbes, — a  non-absorbable  and,  consequently,  an 
insoluble  substance.  I  was  led  to  proceed  in  cholera  as  in 
typhoid  fever.  I  employed  iodoform  in  such  a  state  of  division 
that  the  dose  employed  represented  a  surface  of  sixty  square 
metres;  I  gave  1  gramme  a  day  in  conjunction  with  5  grammes 
of  naphthalin, — a  substance  that  is  almost  insoluble.  I  have  had 
a  mortality  of  66  per  cent., — i.e.,  equal  to  that  of  the  other  hos- 
pitals. This  is  not  a  very  gratifying  result,  but  we  may  learn 
something  from  it. 

What  objection  can  be  raised  to  the  accuracy  of  the  following 
proposition  ?  "  If  the  pathogenic  organism  exists  in  no  other  part 
of  the  system,  and  if  we  have  succeeded  in  destroying  it  in  the 
intestines,  choleraic  accidents  ought  not  to  be  produced."  In  the 
first  place,  it  may  be  urged  that  Koch's  microbe  is  not  influenced 
by  iodoform  or  by  naphthalin.  This  resistance  would  be  sur- 
prising on  the  part  of  an  organism  that  is  more  vulnerable  than 
most  of  the  known  microbes,  since  it  is  killed  by  heat  and  desic- 
cation. Moreover,  I  may  mention  an  experiment  made  by  M. 
Chantemesse,  who  checked  the  germination  of  the  bacilli  by 
introducing  into  the  substance  about  to  be  used  for  their  cultiva- 
tion a  small  quantity  of  the  preparation  administered  to  the 
patients. 

It  may  also  be  said  that  the  treatment  was  instituted  too 
late,  the  morbid  poison  being  already  formed  and  absorbed.  I 


CHOLERA  NOT  THE  RESULT  OF  INTESTINAL  INFECTION.     261 

answer  \>y  facts.  A  certain  number  of  the  patients  subjected  to 
the  antiseptic  treatment  recovered.  I  continued  to  give  them 
iodoform  and  naphthalin  ;  several  of  them  had  a  relapse.  Now, 
these  had  ceased  to  be  influenced  by  the  poison  absorbed  at  first. 
A  fresh  germination  must,  therefore,  have  taken  place  in  the 
system  of  infectious  agents  that  had  remained  in  some  part  of 
the  organism,  but  not  in  the  alimentary  canal,  the  latter  having 
remained  aseptic.  I  conclude  from  this  that  the  germination  of 
the  pathogenic  agent  of  cholera  does  not  take  place  in  the 
intestines. 

While  I  was  attending  the  cholera  patients,  I  also  attended 
typhoid  patients  in  other  wards.  The  latter  having  been  sub- 
jected rigorously  to  iodoform  and  naphthalin,  their  intestines 
were  aseptic,  and  yet  two  of  them  took  the  cholera  in  the  course 
of  the  typhoid  fever,  and  their  evacuations  consisted  of  black 
matter  having  only  the  odor  of  naphthalin.  We  have,  therefore, 
two  series  of  facts  proving  that  cholera  cannot  be  a  surface 
infection  seated  exclusively  in  the  intestinal  cavity.  The  ali- 
mentary canal  is,  in  all  likelihood,  the  channel  through  which  the 
infectious  agent  enters,  this  entrance  being  probably  effected 
through  the  stomach  rather  than  through  the  intestines ;  but  it 
is  not  in  the  alimentary  canal  that  the  multiplication  of  this 
organism  takes  place. 

If  Koch's  theory  is  undermined,  it  is  only  in  one  of  its 
claims.  I  do  not  say  that  the  bacillus  is  not  the  pathogenic 
agent,  but  I  think  that,  if  it  is,  it  must  exist  elsewhere  than 
where  Koch  has  seen  it.  Other  investigators  believe  that  they 
have  succeeded  in  staining  it,  and  in  finding  it  in  various  organs; 
they  have  obtained  cultures  with  fragments  of  the  viscera. 
Whether  the  infectious  germ  in  cholera  is  Koch's  bacillus  or  any 
other,  one  must  exist ;  and  we  should  not  be  justified  in  denying 
its  existence  simply  because  we  have  not  seen  it.  The  microbe 
of  hydrophobia,  which  we  cultivate  in  animals  and  which  we  can 
attenuate  or  intensify,  has  not  yet  been  discovered.  We  may, 
therefore,  proceed,  notwithstanding  the  absence  of  direct  demon- 
stration concerning  its  nature,  and  admit,  in  the  interest  of  both 
prophylaxis  and  therapeutics,  that  cholera  is  an  infectious  disease. 
But,  granting  that  there  must  be  a  certain  pathogenic  agent  in 


262  LECTURES  ON   AUTO-INTOXICATION. 

cholera,  let  us  ask  ourselves  if  this  agent  does  not  produce  some 
substance,  and  if  it  does  not  kill  by  causing  a  kind  of  poisoning. 
This  idea,  which  I  formulated  in  1879,  speaking  of  infectious 
diseases  generally,  has  been  taken  up  by  Klebs  and  Koch,  in 
connection  with  cholera.  It  would  be  necessary  to  show  that 
there  exists  in  the  bodies  of  those  attacked  with  cholera,  or  in 
their  excretions,  a  particular  toxic  substance,  capable  of  repro- 
ducing in  other  living  beings  symptoms  similar  to  those  of 
cholera. 

M.  Gabriel  Pouchet  has  discovered  the  existence  of  an  alka- 
loid in  the  discharges  of  cholera  patients,  and  M.  Hayem  also 
mentions  one.  It  would  have  been  more  satisfactory  if  they  had 
stated  whether  these  were  particular  alkaloids  distinguished  from 
those  which  are  found  normally  in  the  faecal  matter  of  both  the 
sick  and  the  healthy. 

Even  before  these  discoveries,  on  September  20,  1884,  in  the 
case  of  a  rag-picker  suffering  from  cholera,  one  of  that  little  group 
of  individual  cases  that  formed  the  local  epidemic  of  Saint-Ouen, 
the  forerunner  of  the  true  Parisian  epidemic,  I  found,  in  an 
extract  of  575  cubic  centimetres  of  intestinal  matter,  a  consider- 
able quantity  of  an  alkaloidal  substance, — a  quantity  which  cer- 
tainly exceeded  the  proportion  of  alkaloids  generally  contained 
in  faecal  matter.  This  alkaloidal  substance  differed  from  the 
other  intestinal  alkaloids  in  one  of  its  chemical  characteristics. 
If,  like  them,  it  was  precipitated  by  the  iodo-ioduretted  reagent, 
by  the  iodides  of  mercury  and  of  potassium,  by  the  phospho- 
molybdate  of  soda,  by  tungstate  of  soda,  it  did  not  present  the 
reaction  with  tannin.  During  the  epidemic  of  November,  1884, 
I  found  this  alkaloid  again  with  the  same  characteristic.  I  also 
saw  it  crystallized  in  the  form  of  long  and  extremely  fine 
needles ;  but  I  was  not  able  to  experiment  upon  its  physiological 
characteristics,  not  having  been  able  to  obtain  a  sufficient  quan- 
tity of  it.  For  this  reason,  I  thought  it  best  to  leave  the  report 
of  these  observations  among  my  laboratory  notes. 

Another  question  arises  as  regards  this  alkaloid.  Supposing 
it  to  be  a  substance  peculiar  to  cholera  patients,  might  it  not  have 
been  produced  in  some  other  way  than  by  the  action  of  parasitic 
organisms?  I  know  that  in  cholera  patients  matter  is  formed 


SYMPTOMS  PRODUCED   BY   INJECTION   OF   CHOLERAIC  URINE.      263 

differently  from  that  in  other  people,  whether  ill  or  in  good  health. 
Speaking  of  this,  I  may  mention  a  peculiarity  in  connection  with 
naphthalin.  All  my  patients  were  treated  with  this  substance. 
In  some  it  underwent  normal  metamorphoses.  In  others  it 
underwent  unusual  metamorphoses,  which  I  have  also  remarked 
in  acute  yellow  atroph}r  of  the  liver  and  in  two  cases  of  typhoid 
fever.  In  these  latter  cases,  the  urine,  instead  of  retaining  the 
somewhat  dirty,  blackish-brown  tint  which  it  assumes  in  people 
that  have  been  subjected  to  naphthalin,  assumed  spontaneously, 
at  the  moment  of  emission,  a  deep-violet  color,  like  that  of  a 
solution  of  permanganate  of  potass.  It  was  not  the  pink  tint 
that  is  generally  obtained  by  means  of  acetic  acid  in  the  urine 
of  patients  who  were  being  treated  with  naphthalin.  The  violet 
matter  in  choleraic  urine  is  soluble  in  ether,  whereas  that 
which  appears  upon  the  addition  of  acetic  acid  in  the  urine  of 
other  patients  treated  with  naphthalin  will  not  dissolve  in  ether. 
This  anomalous  fact  is  probably  owing  to  certain  changes  in  the 
liver.  Other  substances  besides  naphthalin  might,  therefore,  be 
as  irregularly  transformed,  and  certain  anomalous  substances 
found  in  the  passages  or  in  the  alimentary  canal  of  cholera 
patients  may  have  been  generated  in  the  liver  or  in  the  system 
without  the  intervention  of  microbes.  There  are,  besides,  in 
cholera  patients,  special  toxic  substances,  which  cause  death  in  a 
different  manner  to  the  normal  poisons  of  the  system.  There  is 
a  choleraic  poison  which  is  shown  by  the  special  toxicity  of  the 
urine  of  cholera  patients.  The  experimental  injections  of  the 
urine  of  cholera  patients  rarely  produce  in  animals  the  symptoms 
of  poisoning  by  normal  urine. 

Myosis  is  generally  defective.  Instead  of  appearing  at  the 
tenth  cubic  centimetre,  it  comes  later  or  is  absent  altogether. 
But  one  sign  is  very  soon  observed,  which  is  not  produced  by 
injections  of  any  other  kind  of  urine, — cyanosis,  which  is  shown 
on  the  inner  surface  of  the  ear  in  the  rabbit ;  then  muscular 
cramps,  which  in  no  way  resemble  the  convulsions  produced  by 
other  kinds  of  urine,  being  spasms  which  begin  long  after  the 
commencement  of  the  injection  and  continue  for  half  an  hour 
after  it  has  ceased.  They  consist  of  a  slow  and  protracted 
stretching  of  the  hind-limbs,  followed  by  four  or  five  spasms  at 


264  LECTURES  ON   AUTO-INTOXICATION. 

the  end  of  a  minute  and  a  half,  another  rigid  extension  of  the 
limbs,  and  fresh  spasms ;  eight,  ten,  or  fifteen  similar  contrac- 
tions may  take  place,  and  then  quietness  is  restored. 

Cooling  of  the  surface  is  more  marked  after  the  injection  of 
choleraic  urine  than  with  normal  urine.  Albuminuria  appears  at 
the  commencement  and  is  intense,  whereas  it  is  rare  and  does  not 
appear  till  late  with  normal  urine.  After  the  injection  of  normal 
urine  the  animal  is  restored  to  health  ;  after  the  injection  of  chol- 
eraic urine  it  is  seized  with  pea-soupy  diarrhoea,  the  motions  being 
pale  or  reddish,  without  any  trace  of  bile.  The  albuminuria  goes 
on  increasing;  then,  after  a  day  and  a  half,  anuria  sets  in,  the 
refrigeration  continues  and  is  more  marked,  and  the  animals  die, 
with  a  rectal  temperature  of  33°  or  34°  C.  On  the  bodies  being 
examined,  the  intestine  is  found  to  be  congested  and  filled  with 
pea-soupy,  diarrhoeic  matter,  constituted  mainly  by  the  intes- 
tinal desquamation,  resembling  choleraic  diarrhoea  so  much  that 
it  might  be  mistaken  for  it,  except  that  no  bacilli  are  found. 
Either  the  urine  injected  was  infectious,  or  we  had  obtained  a 
form  of  poisoning  similar  to  that  determined  by  the  infectious 
agent  in  cholera  when  it  has  produced  the  toxic  matter. 


LECTURE  XXX. 

CHOLERA  (CONCLUSION). 

A  special  poison  •  exists  in  the  urines  of  cholera  patients.  The  symptoms  of  the 
animals  into  which  they  are  injected  cannot  be  explained  by  infection.  Effects 
produced  on  animals  by  the  substances  soluble  and  insoluble  in  alcohol  and 
contained  in  choleraic  urine.  The  poison  which  causes  the  choleraic  symp- 
toms in  animals  is  soluble  in  alcohol  anjd  is  organic.  The  second  period  in 
cholera  is  the  result  of  a  fresh  intoxication  occasioned  by  the  normal  poisons, 
from  which  the  kidneys  no  longer  free  the  system  :  it  is  uraemia.  Myosis  in 
cholera  patients  that  are  anuric.  This  terminal  uraemia  in  cholera  diflers 
from  ordinary  uraemia,  as  several  of  the  sources  of  the  ursemic  poisons  are 
suppressed. 

THE  history  of  the  progress  of  cholera  compels  us  to  look 
upon  it  as  an  infectious  disease.  But  it  is  doubtful  whether 
Koch's  pathogenic  agent  is  the  true  one.  Admitting,  from 
analogy,  that  there  is  an  infectious  agent  peculiar  to  cholera,  we 
must  ask  ourselves  whether  the  microbe  is  responsible  for  all  the 
ill  effects  observed,  or  whether,  amongst  the  symptoms  of  the 
illness,  there  may  not  be  toxsemic  accidents  attributable  to  a 
substance  formed  by  the  system  itself,  or  by  the  microbe. 

I  believe  that  this  poison  really  exists,  and  the  study  of  the 
toxic  nature  of  the  urine  in  cholera  patients  has  led  me  to  think 
that  it  is  eliminated  by  the  urine.  The  toxicity  of  choleraic 
urine  presents  special  characteristics.  Besides  the  properties 
which  it  has  in  common  with  normal  urine  (pupillary  contraction, 
weakening  of  the  muscles,  certain  respiratory  disturbances,  fall 
of  temperature,  and  diuresis)  choleraic  urine  produces,  in  the 
animals  into  which  it  is  injected  by  the  intra-venous  method, 
very  marked  cyanosis  on  the  inner  surface  of  the  ear, — a  much 
greater  fall  of  temperature,  lasting  until  death  takes  place ; 
cramps,  which  I  have  never  observed  with  injections  of  other 
kinds  of  urine,  and  which  are  very  different  from  opisthotonos 
and  convulsions, — cramps  which  consist  of  a  long,  slow  exten- 
sion of  the  limbs,  which  is  repeated  at  short  intervals  for  half  an 
hour ;  diarrhoeic  evacuations,  which  may  occur  with  certain  nor- 

(265) 


266  LECTURES  ON   AUTO-INTOXICATION. 

mal  or  pathological  urines  as  with  distilled  water,  but  in  this  last 
case  only  with  enormous  quantities  of  urine,  whereas  a  very  small 
quantity  of  choleraic  urine  produces  motions  of  a  whitish,  yellow- 
ish, grayish,  or  reddish  color,  the  coloring  being  due  to  epi- 
thelial desquamation  of  the  small  intestine  and  to  the  retention 
of  bile  in  the  gall-bladder. 

Albuminuria,  which  is  rare  and  very  slight  with  normal 
urine,  is  in  this  case  always  considerable  or  intense,  lasting 
throughout  the  experimentally-produced  disease.  This  albu-' 
minuria  may  be  succeeded  at  the  last  by  complete  anuria.  At 
length  death  ensues, — not  during  the  injection,  but  after  an  inter- 
val of  from  twelve  hours  to  four  days ;  whereas,  with  animals 
whose  death  is  caused  by  the  injection  of  other  normal  or  patho- 
logical urine,  death  occurs  always  during  the  injection.  With 
choleraic  urine  nearly  all  animals  die ;  in  those  that  survive  we 
may  follow  the  development  of  the  disease.  The  thermometer 
indicates  the  gradual  return  of  heat  production  ;  the  appetite 
does  not  return  for  some  time,  the  albuminuria  diminishes,  and 
complete  recovery  is  not  effected  until  after  about  six  days. 

In  what  light  are  we  to  consider  these  accidents  ?  Are  we 
dealing  with  a  case  of  infection  or  of  experimental  poisoning  ?  I 
have  answered  some  of  the  suppositions  that  might  be  made.  To 
account  for  infection,  the  infectious  agent  must  have  been  in  the 
urine  of  the  patient ;  discharges  containing  bacteria  must  have 
come  from  the  kidneys.  Now,  we  do  not  find  any  microbes  in 
the  urine  of  cholera  patients,  either  by  direct  examination  or 
after  coloration.  It  is  true  that,  in  several  diseases  which  are 
evidently  virulent,  we  cannot  find  microbes  (hydrophobia,  for 
instance),  or  we  can  only  demonstrate  their  existence  by  improved 
methods  of  coloration  (as  in  tuberculosis  or  leprosy).  Thus, 
there  are  microbes  which  remain  invisible  to  us;  the  cholera 
germ  is  perhaps  one  that  calls  for  a  special  technical  treatment 
in  order  to  be  discovered. 

We  might  have  tried  to  obtain  cultures  with  the  urine  of 
cholera  patients.  I  have  not  tried  this,  as  I  was  only  able  to 
obtain  the  urine  of  female  patients;  and  in  their  urine  one  is 
always  liable  to  meet  with  some  of  those  agents  of  infection  which 
germinate  readily  on  the  external  genitals,  the  conditions  of 


INJECTIONS   OF   CHOLERAIC   URINE.  267 

temperature  and  moisture  being  very  favorable  to  their  develop- 
ment. But  these  means  were  not  required  in  order  to  settle  the 
question.  If  the  disease  that  we  communicated  to  animals  by 
intra-venous  injections  of  choleraic  urine  had  taken  the  course 
of  an  infectious  disease,  we  should  have  to  acknowledge  the 
existence  of  a  phase  of  incubation  which  was  altogether  absent. 
We  saw  all  the  symptoms  appear  immediately  after  the  introduc- 
tion of  the  urine  and  continue  their  course  without  any  interrup- 
tion. This  total  absence  of  incubation  is  a  decisive  argument. 
Moreover,  if  the  disease  that  we  produced  was  of  an  infectious 
nature,  the  quantity  of  urine  injected  would  be  of  little  impor- 
tance ;  the  infectious  germs,  by  their  multiplication,  would  always 
produce  the  same  symptoms,  whatever  the  quantity  of  choleraic 
urine  introduced  into  the  system.  Now,  this  was  not  the  case : 
we  always  observed  an  exact  proportion  between  the  quantity  of 
urine  injected  and  the  gravity  of  the  disease. 

Two  animals  survived,  having  been  subjected  to  an  injection 
of  only  12  cubic  centimetres.  All  of  those  that  died  received 
more  than  17  cubic  centimetres,  and  some  as  much  as  90  cubic 
centimetres.  From  the  two  reasons  given  above,  I  conclude  that 
the  experimentalty-produced  disease  resulting  from  injections  of 
choleraic  urine  is  of  a  toxic  nature. 

I  evaporated  all  the  water  from  some  choleraic  urine  and 
obtained,  by  the  processes  that  I  employ  with  normal  urine,  two 
extracts, — one  containing  the  substances  that  are  soluble  in 
alcohol,  the  other  those  that  are  insoluble  in  alcohol.  I  poisoned 
some  animals  with  these  two  extracts,  but  the  results  observed 
were  not  the  same  in  both  cases.  After  the  injection  of  the  alco- 
holic extract  of  normal  urine  we  observe  salivation,  coma,  and 
death,  if  the  quantity  injected  is  sufficient ;  if  not,  the  animal  is 
restored  to  health  in  less  than  half  an  hour. 

With  the  alcoholic  extract  of  choleraic  urine  we  rarely  obtain 
salivation ;  we  sometimes  get  somnolence,  but  the  animals  do 
not  recover.  They  have  albuminuria  and  diarrhoea,  and  die 
within  two  days.  These  last  accidents — albuminuria,  colorless 
diarrhoea,  and  death  in  two  days — are  the  same  as  those  pro- 
duced by  the  injection  of  choleraic  urine  itself.  But  I  did  not 
obtain  cyanosis  and  cramps  with  the  alcoholic  extract  alone. 


268  LECTURES  ON   AUTO-INTOXICATION. 

With  the  aqueous  extract  containing  the  substances  that  are 
insoluble  in  alcohol  I  observed,  as  with  normal  urine,  myosis  and, 
when  the  quantity  was  sufficient,  convulsions,  but  these  last  in 
no  way  resembled  the  spasms  produced  by  the  urine  of  cholera 
patients.  Lastly,  in  order  to  produce  death,  larger  quantities 
of  the  aqueous  extract  were  required  than  of  the  choleraic  urine 
itself.  When  death  occurred,  it  was  always  immediate,  never 
delayed.  I  never  observed  either  albuminuria  or  diarrhoea,  and 
all  the  animals  that  survived  were  restored  to  health  after  this 
short  toxic  illness  of  half  an  hour's  duration. 

Thus,  there  exists  in  choleraic  urine  something  which  is 
carried  off  by  alcohol,  and  which  is  different  from  the  substances 
generally  found  in  urine, — something  which  can  be  separated 
from  the  other  parts ;  in  short,  a  special  morbid  poison.  Amongst 
the  toxic  accidents  caused  by  the  alcoholic  extract  of  choleraic 
urine  we  note  the  absence  of  cramps.  Are  we  mistaken  in 
attributing  them  to  the  cholera  poison?  Besides  the  special 
features  belonging  to  cholera  poisoning,  might  not  the  cramps 
be  caused  by  the  substance  that  gives  the  urine  its  convulsive 
property,  viz.,  potass  ?  But  choleraic  urine  produces  cramps  at 
17  cubic  centimetres  per  kilogramme  of  the  animal.  I  evaporated 
400  cubic  centimetres  of  choleraic  urine ;  the  extract  was  reduced 
to  ashes  and  the  residuum  washed  in  distilled  water,  which 
carries  off  all  the  potass.  Now,  the  whole  of  the  aqueous  liquid 
obtained  was  injected  little  by  little,  without  producing  any 
toxic  phenomena  or  convulsions. 

Thus,  there  is  in  choleraic  urine  a  poison  which  is  a  soluble 
organic  substance,  and  which  I  call  the  choleraic  poison.  I 
cannot  either  name  or  define  this  poison  chemically  ;  I  only  know 
it  by  its  physiological  properties.  I  do  not  know  whether  it  is 
formed  by  the  diseased  organism  carrying  on  the  work  of  elab- 
oration defectively,  or  by  microbes, — whether  it  is  produced  by 
the  patient  himself,  or  by  the  vegetable  parasites  that  have 
caused  the  disease. 

I  cultivated  in  my  laboratory  Koch's  comma  bacillus.  I  had 
at  my  disposal  a  considerable  quantity  of  pure  culture-liquid, 
and  I  endeavored  to  solve  the  two  following  questions:  1. 
Does  the  comma  bacillus  determine  in  the  liquid  the  formation 


CULTURES   OF   THE   COMMA   BACILLUS   ARE    NON-TOXIC.  269 

of  a  toxic  substance  ?  2.  Does  the  comma  bacillus  really  possess 
a  special  pathogenic  property, — i.e.,  does  inoculation  with  it 
produce  in  animals  the  appearance  of  cholera  ? 

In  order  to  answer  the  first  question,  I  made  several  experi- 
ments. I  inoculated  by  the  subcutaneous  method  some  guinea- 
pigs,  weighing  on  an  average  550  grammes,  with  from  3.8  to  35 
cubic  centimetres  of  the  undiluted  liquid  in  which  comma  bacilli 
had  been  cultivated.  These  animals  experienced  no  morbid 
symptoms.  In  the  second  instance  I  introduced  under  the  skin 
of  another  guinea-pig,  weighing  575  grammes,  20  cubic  centi- 
metres of  the  liquid  heated  to  63°  C.  Neither  at  the  time  of 
the  inoculation  nor  after  it  did  the  animal  seem  affected  in  any 
appreciable  degree.  Proceeding  with  the  solution  of  this  first 
question  that  I  had  asked  myself,  and  wishing  to  employ  the 
intra-venous  method,  I  experimented  on  the  rabbit.  I  injected 
into  the  veins  of  the  ear  of  a  rabbit,  weighing  1800  grammes,  79 
cubic  centimetres  of  the  culture-fluid,  which  had  neither  been 
heated  nor  filtered  from  the  bacilli, — that  is,  43  cubic  centimetres 
per  kilogramme.  At  the  moment  of  the  experiment  the  only 
effect  shown  by  the  animal  was  accelerated  respiration,  especially 
at  the  end  of  the  injection.  It  died  twenty-four  hours  afterward. 
The  post-mortem  examination  showed  pulmonary  congestion, 
slight  diarrhoea,  somewhat  intense  albuminuria,  the  absence  of 
comma  bacilli  in  the  excrement,  and  the  presence  of  some  of 
these  bacilli  in  the  kidneys,  to  which  the  blood,  having  received, 
had  conveyed  them.  Altogether,  the  symptoms  observed,  and 
especially  the  interval  of  time  that  elapsed  between  the  injection 
and  death,  suggested  infection,  and  not  poisoning.  Lastly,  an- 
other rabbit,  weighing  1990  grammes,  received  in  the  veins  of 
the  ear  in  five  minutes  92  cubic  centimetres  of  the  liquid,  which 
had  been  heated  and  filtered  from  the  bacilli,  or  46  cubic  centi- 
metres per  kilogramme.  The  temperature  fell  eight-tenths  at  the 
moment  of  the  experiment,  but  the  animal  showed  no  other  sign 
of  disturbance,  and  it  afterward  continued  in  good  health.  These 
experiments,  which  I  describe  briefly,  enable  me  to  dispense 
with  long  arguments.  They  fully  justify  me  in  giving  a  negative 
answer  to  the  first  question :  the  liquids  in  which  the  comma 
bacilli  are  cultivated  contain  no  substance  of  a  toxic  nature. 


270  LECTURES   ON   AUTO-INTOXICATION. 

In  order  to  answer  the  second  question, — as  to  whether  the 
comma  bacillus  is  capable  of  producing  cholera  in  animals, — I 
experimented,  like  Koch,  on  guinea-pigs.  Like  Koch,  I  intro- 
duced into  the  stomach  of  my  guinea-pigs  11  cubic  centimetres 
of  the  liquid,  after  having  first,  according  to  the  German  scien- 
tist's method,  alkalized  the  stomach  by  means  of  5  cubic  centi- 
metres of  a  5-per-cent.  solution  of  carbonate  of  soda,  and  arrested 
all  motion  in  the  intestine  by  the  intra-peritoneal  injection  of  3 
cubic  centimetres  of  tincture  of  opium.  I  must  own  that  the 
results  I  obtained  were  the  same  as  those  obtained  by  Koch 
himself.  My  guinea-pigs  soon  died.  After  death  I  found  that 
the  stomach  was  in  most  cases  dilated,  that  the  small  intestine 
contained,  more  or  less  abundantly,  diarrhoeic  matter,  and  that 
there  were  comma  bacilli,  in  varying  quantities,  to  be  observed 
in  this  material.  But  I  also  instituted  other  experiments  :  with 
some  other  guinea-pigs  I  alkalized  the  stomach  and  checked  the 
action  of  the  intestine  exactly  according  to  Koch's  method  and 
as  I  had  done  in  the  experiment  just  described.  But  in  this 
second  experiment,  instead  of  using  the  same  kind  of  liquid  as 
before,  I  introduced  into  some  of  the  guinea-pigs  11  cubic  centi- 
metres of  an  old  charbon  culture-fluid  and  into  others  11  cubic 
centimetres  of  liquid  that  had  been  turned  acid  by  exposure  to 
the  air,  or  some  old  pyocyanic  culture-fluid.  Well,  the  animals 
died  almost  as  rapidly  as  those  that  had  received  the  comma 
bacilli,  presenting  almost  the  same  symptoms,  except  that  the 
diarrhoea  was  less  abundant.  These  last  results  singularly  de- 
tract from  the  value  of  the  first  series  of  experiments;  and, 
without  denying  that  the  comma  bacillus  has  any  pathogenic 
property,  we  are,  in  my  opinion,  justified  in  asserting  that  this 
pathogenic  property  has  not  yet  been  clearly  demonstrated. 

If,  then,  judging  by  its  analogy  to  other  infectious  diseases, 
and  by  the  history  of  its  migrations  and  of  its  localized  centres, 
I  am  led  to  admit  that  cholera  is  caused  by  infection,  I  am  also 
justified  in  saying  that,  side  by  side  with  the  infection,  there  ex- 
ists in  the  pathogeny  of  cholera  a  secondary  poisoning  conse- 
quent upon  infection.  I  think  that  the  symptoms  which  are 
considered  characteristic  of  cholera,  and  which  enable  us  to  form 
the  diagnosis,  are  the  results  of  this  poisoning.  It  is  to  this 


THE   URAEMIA   OF   CHOLERA.  2tl 

cause  that  we  must  attribute  cyanosis,  refrigeration,  respiratory 
disturbance,  hiccough,  the  peculiar  form  of  diarrhoea,  intestinal 
desquamation,  cramps,  dehydration  of  the  tissues,  albuminuria, 
and  anuria.  These  are  the  symptoms  of  cholera  poisoning,  and 
I  may  add  to  the  list  the  preservation  of  consciousness  and  the 
absence  of  pupillary  contraction. 

But  soon  a  second  poisoning  supervenes,  which  is  associated 
with  the  first  or  alternates  with  it ;  it  takes  the  clinical  form  of 
mental  torpor,  loss  of  consciousness,  somnolence,  and  coma.  The 
respiratory  rhythm  changes  ;  it  becomes  that  of  uraemia,  or  what 
is  known  as  the  Cheyne-Stokes  respiration.  The  temperature  is 
affected,  sometimes  rising  and  sometimes  remaining  low.  At  the 
same  time  the  pupils  contract  and  become  punctiform. 

Is  not  this  series  of  symptoms  very  different  from  that  of  the 
earlier  period ;  and  does  it  not,  therefore,  spring  from  another 
kind  of  poisoning?  We  observe  all  these  symptoms  when 
anuria  and  myosis  appear,  and  they  are  all  to  be  found  in  the 
clinical  picture  of  uraemia.  Among  authors  I  have  not  found 
any  indication  bearing  upon  this  fact.  I  was  myself  ignorant  of 
it  until  the  day  when  this  coincidence  between  the  suppression 
of  the  urinary  secretion  and  the  appearance  of  those  symptoms, 
the  existence  of  which  I  knew  to  be  in  uraemia,  stood  clearly  out 
before  me. 

This  uraemia  of  the  second  phase  of  cholera  is  not  the  ordi- 
nary uraemic  intoxication  by  poisons  produced  from  four  sources ; 
we  cannot  in  this  case  attribute  it  to  alimentation,  or  to  intes- 
tinal putrefactions,  or  to  biliary  re-absorption,  since  there  is  no 
jaundice  at  the  time,  and  the  absorption  cannot  be  effected  by 
the  intestine.  The  poison  in  this  case  comes  from  disassimilation. 

This  uraemic  period  has  long  been  designated  the  period  of 
reaction,  the  external  temperature  being  higher, — i.e.,  equilibrium 
being  established  between  the  rectal  and  peripheral  temperatures, 
— a  singular  reaction,  in  which  torpor  appears  instead  of  spasms, 
and  in  which  we  can  only  see  inertia  of  the  whole  nervous  system  I 
It  is  a  perversion  of  the  meaning  of  the  word  to  apply  such  a 
name  to  this  phase  of  the  disease.  It  has  also  been  termed  the 
typhoid  phase,  and  the  period  of  typhoid  reaction, — a  designation 
that  is  certainly  less  open  to  criticism,  for  in  the  condition  of 


272  LECTURES   ON    AUTO-INTOXICATION. 

the  patients  there  is  certainly  something  that  reminds  us  of 
typhoid  fever.  But  the  pathogenic  conditions  are  not  abso- 
lutely the  same.  In  cholera  patients  whose  intestines  are  sub- 
jected to  antiseptic  treatment  there  is  no  intestinal  putrefaction  ; 
they  experience  poisoning  by  disassimilation  only.  It  was 
therefore  asserted  that  this  phase  of  cholera  must  be  considered 
a  uraemic  period.  There  was  no  need  to  wait  for  pupillary  con- 
traction in  order  to  detect  signs  of  uraemia ;  the  blood  and  the 
tissues  were  analyzed,  and  extractive  matter  and  urea  were  found 
accumulated  in  them  in  considerable  quantities  (1  gramme  20 
centigrammes  and  1  gramme  30  centigrammes  of  urea  per  kilo- 
gramme of  muscular  tissue).  This  period  can  be  foreseen  when 
anuria  sets  in ;  after  pupillary  contraction  it  can  be  affirmed. 
In  all  patients  seized  with  anuria  myosis  occurs ;  I  have  observed 
it  in  every  case ;  this  is  a  clinical  fact  which,  in  my  opinion,  is  of 
some  importance. 

If  we  do  not  find  in  the  uraemia  following  cholera  all  the 
symptoms  usually  observed  in  ordinary  uraemic  poisoning,  it  is. 
because  several  of  the  sources  of  the  uraemic  poisons  are  sup- 
pressed. Disassimilation  may  supply  the  narcotic  poison  as 
well  as  the  convulsive  poison.  When  potass  is  sent  into  the 
blood  in  excess  it  causes  convulsive  uraemia ;  but  if  convulsive 
uraemia  is  not  generally  observed  in  the  uraemic  phase  of  cholera, 
we  can  understand  why  not.  The  rapid  and  premature  dehydra- 
tion has  drawn  off  with  the  water  all  the  potass  of  the  fluids 
and  a  portion  of  that  in  the  anatomical  elements ;  thus,  when 
the  period  of  excessive  destruction  of  matter  arrives,  potass  and 
mineral  substances  are  not  so  superabundant  in  the  blood  as 
organic  and  extractive  substances.  In  a  case  that  I  have  already 
quoted,  there  was  so  little  potass  that  an  extract  of  400  grammes 
of  the  patient's  urine  did  not  cause  convulsions  in  an  animal. 
We  see  that  cholera  furnishes  us  with  an  example  of  double 
self-poisoning :  first,  by  an  anomalous  product  (this  is  cholera 
poisoning,  properly  so  called);  second,  by  normal  products 
(this  is  a  variety  of  uraemic  poisoning).  Moreover,  the  study 
of  cholera  corroborates  the  theory  that  anomalous  substances 
may  exist  in  some  diseases,  and  that  morbid  poisons  are  not  a 
dream. 


LECTURE  XXXI. 
THE  GENERAL  THERAPEUTICS  OF  SELF-POISONING. 

The  course  to  be  pursued  is  to  prevent  the  poisons  being  formed  ;  to  oppose  their 
penetration  into  the  system ;  if  they  have  been  absorbed,  to  try  to  destroy 
them  or  to  stimulate  the  action  of  the  liver,  which  is  a  physiological  destroyer 
of  poisons  ;  lastly,  to  encourage  the  elimination  of  poisons  by  the  skin,  the 

lungs,  the  intestines,  and  the  kidneys. Sudorifics,  purgatives,  diuretics, 

bleeding,  inhalations  of  compressed  air  and  oxygen  ;  intra-venous  injections 
of  antiseptic  remedies. 

Is  it  possible  to  make  any  therapeutic  application  of  the 
knowledge  that  we  have  acquired  with  regard  to  the  pathogeny 
of  self-poisoning?  The  first  course  to  take  is  to  prevent  the 
poison  being  formed.  When  once  it  is  formed,  we  must  endeavor 
to  oppose  its  penetration  into  the  S3rstem  by  preventing  its 
absorption.  This  can  be  realized  in  certain  cases  ;  certain  toxic 
substances  are  naturally  precipitated  in  the  intestines,  and  others 
may  be  fixed  by  charcoal,  which  retains  them  physically.  If  the 
poison  has  been  absorbed,  we  must  endeavor  to  destroy  it.  We 
have  found  that  the  liver  has  the  power  of  arresting  poisons ;  it 
withdraws  them  from  the  intestine  and  eliminates  or  -destroys 
them.  We  should  therefore  stimulate  its  action  by  certain  thera- 
peutic treatment.  Lastly,  if  the  poison  has  escaped  the  action 
of  the  liver  it  should  be  eliminated  by  the  skin,  the  lungs,  the 
intestines,  and  the  kidneys. 

If  all  these  attempts  should  fail,  we  must  have  recourse  to 
certain  antidotes  which  tend  to  counteract  the  physiological 
effects  of  the  poisons  that  menace  the  system.  We  have  a 
striking  example  of  the  antagonistic  properties  of  poisons  in 
atropine  and  pilocarpine.  This  side  of  the  question  has  so  far 
merely  been  sketched  out.  We  have,  however,  indicated,  from  a 
pathogenic  point  of  view,  the  existence  of  poisons  that  are  allied  or 
opposed  to  one  another;  in  poisoning  by  substances  in  the  urine, 
I  have  shown  how  the  action  of  the  narcotic  material  prevents 
that  of  the  convulsive  poisons.  The  knowledge  of  these  facts 
shows  us,  at  any  rate,  that  we  should  not  give  up  the  contest.  In 

is  (273) 


274  LECTURES  ON  AUTO-INTOXICATION. 

any  case,  we  must  never  neglect,  in  auto-intoxication,  to  keep  up 
the  strength  of  the  patient,  so  that  he  may  have  time  to  eliminate 
the  poison.  Sometimes  we  only  require  to  keep  him  alive  a  few 
minutes  more  in  order  to  save  him ;  we  cannot  supply  him  with 
radical  force,  but  what  he  requires  is  active  force.  Thus  we  are 
led  to  administer  not  tonics,  but  stimulants,  which  may  awaken 
some  force  remaining  latent. 

The  therapeutic  treatment  is  effected,  to  a  certain  extent,  by 
nature,  or  a  portion  of  it  is  carried  out  by  our  organs  ;  in 
uraemia,  one  of  the  sources  of  poisoning  is  already  lessened,  dis- 
assimilation  being  checked  by  the  disease  itself  in  uraemic  and 
other  patients  attacked  with  self-poisoning.  Poisoning  by 
substances  of  alimentary  origin  may  be  diminished.  If  potass 
really  kills,  the  diminution  of  solid  ingesta  diminishes  the  poison- 
ing ;  now,  these  patients  still  drink,  but  no  longer  eat.  They  must 
not  take  broths  which  contain  the  mineral  elements  of  meat.  The 
poisons  of  the  secretions  are  opposed  to  each  other,  both  naturally 
and  physiologically.  The  system  itself  exercises  prophylactic 
action.  The  bile  which  is  not  eliminated  by  the  intestine  is  pre- 
cipitated. Of  the  poisons  which  it  contains,  one,  which  is  emi- 
nently poisonous, — the  coloring  matter, — is  precipitated  when 
brought  into  contact  with  acid  chyme ;  the  other — the  biliary  salts 
— is  transformed  and  brought  to  the  condition  of  dyslysin.  In 
this  way  man  lives,  thanks  to  the  therapeutics  which  the  system 
exercises  incessantly  upon  itself. 

The  substances  which  are  generated  in  the  intestine  by  putre- 
faction, and  which  are  neither  precipitated  nor  eliminated,  pass 
on  into  the  blood ;  but  a  natural  effort  to  stop  them  is  made  by 
the  liver,  which  partly  prevents  them  from  penetrating  into  the 
general  circulation.  From  this  point  of  view,  there  is  a  great 
difference  between  poisoning  through  the  digestive  channels  and 
that  which  is  effected  by  intra-venous  or  subcutaneous  processes. 
I  know  a  patient  who  takes  daily  20  grammes  of  laudanum 
without  ill  effects.  Is  this  because  the  poison  is  eliminated 
through  the  urine  ?  If  so,  this  should  be  poisonous.  But  it  is 
not ;  it  kills  only  in  the  proportion  of  64  cubic  centimetres  per 
kilogramme.  I  might  conclude  that  the  poisons  of  the  opium 
have  been  destroyed,  but  in  stating  this  conclusion  I  must  make 


ELIMINATION   OF   POISONS.  275 

the  most  express  reservations,  for  a  rabbit  shows  itself  almost  as 
refractory  to  intoxication  by  opium  as  to  poisoning  by  belladonna. 
In  my  opinion,  the  reason  why  this  patient  has  not  been 
poisoned  is  because  I  have  introduced  the  poison  through  the 
intestine.  I  must  remind  you  of  the  facts  observed  by  Schiff 
with  regard  to  the  protective  function  of  the  liver, — facts  which 
Messrs.  Charrin  and  Roger  have  recently  verified  hi  my  labora- 
tory. But  still  the  true  protecting  agent  of  the  system  is  the 
kidney. 

If  I  have  once  more  returned  to  the  many  physiological 
actions  which  tend  to  neutralize  and  expel  poisons,  it  is  in 
order  to  show  more  clearly  how  therapeutic  treatment  may  com- 
plete the  task  of  deliverance  commenced  by  the  system.  As  far 
as  the  alimentary  canal  is  concerned,  I  have  shown  that  we  can 
expel  the  contents  of  the  intestine,  precipitate  with  charcoal  and 
fix  certain  poisons,  and  even  suppress  the  formation  of  poison- 
ous matter  by  instituting  intestinal  antiseptic  treatment. 

I  have  mentioned  bleeding,  which  can  curry  oil'  in  one  opera- 
tion, by  the  abstraction  of  32  grammes  of  blood,  more  poisonous 
matter,  it  is  said,  than  100  litres  of  perspiration.  I  have  sketchi-d 
out  the  physiological  compensations  for  the  action  of  poisons  that 
can  be  obtained  by  the  help  of  chloroform,  chloral,  bromide  (of 
sodium),  diffusible  stimulants,  alcohol,  and  injections  of  ether. 

In  most  diseases  the  morbid  poison  is  a  natural  one,  and 
the  ataxic  or  adynamic  accidents  of  pyretic  diseases  are  the  con- 
sequence of  febrile  oliguria ;  these  are  auto-intoxications  resulting 
from  more  intense  disassimilation,  or  from  more  rapid  cell-de- 
struction, which  sets  at  liberty  imperfectly-oxidized  nitrogenous 
matter  and  an  excess  of  potass.  We  should,  therefore,  by 
stimulating  the  renal  discharge,  hasten  the  elimination  of  this 
excess  of  poison  that  has  been  sent  into  the  circulation. 

In  cases  which  are  certainly  more  rare,  but  the  number  of 
which  will  be  increased  perhaps  when  we  shall  hnvr  prm-li-rUnl 
further  into  the  secrets  of  the  pathogenic  processes,  in  cases 
where  a  morbid  poison  is  really  formed  by  perversion  of  tin-  nu- 
tritive functions,  we  must  endeavor  to  prevent  the  formation  of 
this  poison.  If  it  is  formed  in  the  tissues,  will  this  be  possible  ? 
It  has  always,  up  to  now,  been  said  that  we  cannot  act  upon 


276  LECTURES  ON   AUTO-INTOXICATION. 

poisons  which  have  impregnated  the  system.  But,  in  the  first 
place,  without  speaking  of  poisons  of  interstitial  origin,  there 
are  those  which  may  be  formed  on  accessible  surfaces.  Already, 
in  some  cases,  we  are  able  to  effect  a  rapid  cure  of  the  suppura- 
tion in  abscesses,  fistulae,  and  empyemata. 

We  know  how  to  encourage  the  elimination  of  the  poison, 
and  to  prevent  its  continuation  by  drainage,  washing,  and  the 
attitude  in  which  the  patient  is  placed.  We  draw  off  mechan- 
ically the  putrid  products,  and  contend  against  putrefaction 
in  the  accessible  natural  cavities, — the  vagina,  the  uterus,  and 
the  intestines.  In  such  cases,  antiseptic  remedies  bring  about 
an  improvement  at  once:  a  sudden  fall  of  temperature,  a  dimi- 
nution in  the  dryness  of  the  mouth,  and  alterations  of  the  car- 
diac rhythm.  In  diseases  caused  by  eating  bad  food,  in  severe 
putrid  diarrhoea,  provided  that  the  treatment  is  instituted 
before  the  occurrence  of  secondary  accidents  and  the  establish- 
ment of  metastatic  centres,  we  can  really  effect  a  cure ;  but,  if 
we  have  not  succeeded  in  preventing  the  formation  of  poisons, 
we  cannot  depend  upon  the  protection  of  the  liver,  unless  it  is 
interposed  between  the  source  of  the  poisons  and  the  other 
organs.  This  condition  only  exists  in  poisoning  of  intestinal 
origin.  It  is  true  that  a  portion  of  the  poisons  absorbed  will 
pass  back  into  the  liver  with  the  blood  of  the  general  circula- 
tion, but  this  will  only  be  a  very  small  fraction  instead  of  the 
whole. 

I  very  much  doubt  whether  we  shall  ever  know  that  the 
function  of  the  liver  can  be  stimulated  by  medicinal  treatment, 
and  whether  the  employment  of  purgatives,  in  intoxications  that 
are  not  produced  through  the  intestines,  can  thus  be  justified. 
In  toxaemia  from  intestinal  poisons,  the  utility  of  purgatives 
is  explained  in  quite  another  way ;  they  expel  the  poison 
mechanically. 

What  can  we  do  against  poisons  in  the  circulation  ?  Endeavor 
to  eliminate  them.  In  all  ages  the  course  adopted  has  been  to 
increase  the  action  of  the  various  emunctories  of  the  body. 
To  provoke  perspiration  was  the  alpha  and  omega  of  the  thera- 
peutic treatment  of  antiquity.  Hot  or  warm  drinks,  wrapping 
in  hot  linen  or  wet  sheets,  the  administration  of  Dover's  powder 


DIAPHORESIS  AND  BLEEDING.  277 

have  all  been  employed  with  the  object  of  acting  upon  the  hu- 
mors. I  am  inclined  to  think  that  the  result  of  perspiration  is 
not  beneficial,  since  perspiration  lessens  the  urine,  which  carries 
out  of  the  system  so  many  toxic  products.  If  in  former  times 
it  was  thought  advisable  to  provoke  "perspiration,  it  was  not  used 
so  much  in  cases  of  poisoning  in  order  to  eliminate  the  poison 
as  in  cases  in  which  a  dynamic  action,  such  as  the  dilatation  of 
the  cutaneous  capillaries,  might  relieve  the  centres  ;  and  when  in 
our  own  times  we  have  thought  it  advisable  to  produce  copious 
perspiration  with  pilocarpine,  we  have  not  found  the  general 
condition  improved.  It  is  true  that  perspiration  may  help  to 
eliminate  certain  toxic  substances,  but  the  true  depuration  of 
the  system  is  accomplished  chiefly  through  the  kidneys.  It  is 
the  kidneys  that  enable  the  body  to  be  thoroughly  cleansed,  and 
this  is  effected  by  increasing  the  renal  secretions  by  cold  drinks 
and  cold  bathing. 

When  in  typhoid  patients  the  quantity  of  urine  rises  from 
500  grammes  to  several  litres  and  the  result  is  an  improvement, 
it  is  very  probable  that  this  is  owing  to  the  expulsion  of  toxic 
matter  through  the  urinary  passages.  Lastly,  we  must  not 
omit  the  intestinal  outlet,  which  may  be  acted  upon  by  judicious 
drastic  treatment. 

Bleeding  is  of  use  only  in  toxaemia  attended  with  anuria  and 
serious  impermeability  of  the  kidneys.  Perhaps  it  is  possible  to 
do  something  more  to  destroy  the  poison  or  prevent  its  formation. 
I  have  told  you  in  what  proportions  compressed  air  diminishes 
urinary  toxicity.  This  may  be  explained  in  two  ways  :  either 
disassimilation,  taking  place  in  presence  of  a  greater  proi>ortion 
of  oxygen,  gives  rise  to  more  completely  oxidized  products, 
which  are  less  toxic,  or  the  corpuscles,  having  more  oxygen  at 
their  disposal,  destroy  in  the  blood  a  greater  mass  of  poison. 
Hence  the  utility,  which  is,  perhaps,  somewhat  theoretical,  of 
compressed  air  or  inhalations  of  oxygen. 

If  these  methods  fail,  we  can  only  have  recourse  to  antidotes 
the  properties  of  which  we  have  learned  empirically  ;  in  ataxo- 
adynamic  fevers,  opium,  musk,  and  sometimes  chloral,  which  can 
neutralize  certain  poisonous  effects ;  diffusible  stimulants,  al- 
cohol, coffee,  injections  of  ether.  Even  if  the  morbid  poison  is 


2t8  LECTURES  ON   AUTO-INTOXICATION. 

formed  by  microbes  within  the  organs,  we  are  not  justified  in 
saying  that  it  is  impossible  to  oppose  its  development.  At  any 
rate,  I  have  attempted  this  impossibility.  In  my  trials  of  gen- 
eral antiseptic  treatment,  I  had  to  turn  my  attention  to  sub- 
stances capable  of  arresting  life  in  the  infectious  agents  and 
rendering  the  activity  of  the  microbes  less  intense.  I  had  to 
adopt  the  intra-venous  mode  of  injection  for  these  substances ;  for 
the  absorption  is  so  slow  by  the  subcutaneous  or  intestinal  method, 
and  the  elimination  through  the  emunctories  so  rapid,  that  the 
antiseptic  agent  would  not  have  time  to  impregnate  the  whole 
system.  Observe  that  in  all  that  I  am  saying  there  is  nothing 
that  should  at  present  be  applied  to  the  therapeutic  treatment  of 
man;  but  I  am  justified  in  seeking,  by  experiments  on  animals, 
the  solution  of  problems  which  so  deeply  concern  the  future  of 
medicine.  In  order  to  try  general  antiseptic  treatment  by  the 
intra-venous  method,  it  was  necessary  to  attack  first  those  dis- 
eases in  which  the  microbe  exists  exclusively  in  the  blood.  The 
objection  will  perhaps  be  raised  that  the  pathogenic  agents  of 
infectious  maladies  do  not,  as  a  rule,  inhabit  the  blood  ;  this 
would,  however,  be  to  forget  recurrent  fever,  charbon,  or  malig- 
nant pustule.  But,  to  speak  only  of  the  infectious  diseases  of 
animals,  if  my  attempts  failed  when  directed  against  Charrin's 
septicaemia,  I  obtained  some  encouraging  results  when  treating 
bacteridian  charbon. 

Last  year  I  made  out  a  list  of  some  of  the  substances  that 
may  be  utilized  for  general  antiseptic  treatment.  Of  these  I  will 
only  discuss  mercury.  For  my  experiments  I  chose  the  bin- 
iodide  of  mercury,  the  most  antiseptic,  but  not  the  most  toxic 
of  the  salts  of  mercury.  The  therapeutic  equivalent  of  the  iodide 
of  mercury  is  2  milligrammes.  If  we  exceed  this  quantity  we 
jwovoke  protracted  albuminuria.  This  quantity  is  dissolved  by 
means  of  an  equal  quantity  of  iodide  of  sodium  in  from  5  to  12 
cubic  centimetres  of  water. 

I  will  now  give  the  resume  of  the  trials  of  general  antiseptic 
treatment  that  I  made  with  iodine  and  mercury.  The  greater 
number  of  the  animals  attacked  with  bacteridian  charbon  that  I 
treated  with  injections  of  biniodide  of  mercury  died.  Never- 
theless, when  we  effected  the  inoculation  of  the  bacteria  not 


GENERAL  ANTISEPSIS.  279 

under  the  skin,  but  in  the  blood  in  the  veins,  these  animals  lived 
longer  by  several  hours,  even  a  day  longer.  Moreover,  when  the 
animals  died  we  no  longer  found  any  bacteria  in  their  blood,  nor 
in  cultivations  of  their  organs,  and  the  inoculations  made  with 
their  blood  were  negative.  Why,  then,  did  they  die  ?  No  doubt 
because  they  were  not  able  to  bear  the  double  attack  of  the  ex- 
perimental disease  and  the  treatment ;  but  they  no  longer  had 
charbon.  At  length,  after  a  series  of  failures,  one  animal  recov- 
ered, and  this  animal,  on  being  re-inoculated  twelve  days  after, 
did  not  contract  charbon.  This  is  certainly  only  one  fact,  but  I 
may  say  that  it  is  full  of  promise,  and  this  single  fact  enables  us 
to  believe  that  general  antiseptic  treatment  is  not  merely  a  vain 
dream,  or  a  therapeutic  chimera. 


LECTURE  XXXII. 

GENERAL  RECAPITULATION. 

HAVING  arrived  at  the  end  of  this  study  of  the  part  played 
by  auto-intoxication  in  disease,  it  will  be  to  our  advantage  to  take 
a  rapid  survey  of  the  knowledge  that  we  have  acquired,  and  we 
will  therefore  devote  the  last  of  these  lectures  to  this  recapit- 
ulation. 

We  found,  in  the  first  place, -that  disease  may  spring  from 
four  main  sources.  Man,  as  we  have  said,  contains  in  himself 
the  cause  of  many  diseases.  His  life  may  not  be  normal,  or, 
to  express  the  same  idea  in  other  words,  his  nutrition  may  be 
defective.  This  impaired  nutrition  may  have  been  inherited, 
or  he  may  be  the  victim  of  acquired  nutritive  disorders.  Thus, 
disease  may  arise  from  derangement  of  the  nutritive  functions. 
The  human  organism  may  be  disordered  through  external  causes, 
— mechanical,  physical,  or  chemical.  To  give  an  example  of  each 
of  these  causes,  we  may  mention  bodily  injuries,  burns,  and 
poisoning.  These  causes  reach  the  cells  directly  and  provoke 
their  immediate  reaction.  I  must  own  that  this  pathogenic 
process  rarely  remains  in  a  condition  of  simplicity,  and  that 
often  it  is  rendered  more  complex  by  nervous  reflex  action  or  by 
infection.  External  causes,  in  fact,  may  also  exercise  an  indi- 
rect influence  upon  us  through  the  medium  of  the  nervous 
system;  it  is  through  this  fresh  pathogenic  process  that  the 
diseases  are  developed  which  I  have  called  diseases  induced 
through  nervous  reactions.  Lastly,  our  bodies  may  be  attacked 
by  parasites  and  become  diseased  through  infection. 

Poisoning,  at  its  inception,  comes  under  one  of  these  great 
pathogenic  groups;  but  the  other  processes — the  preliminary 
disorders  of  the  nutritive  functions,  as  well  as  nerve-reactions  and 
infection — may  also  act  in  a  secondary  manner  by  intoxication. 
When  nutrition  is  lessened,— as  in  obesity  and  gout,  for  in- 
stance,— we  frequently  observe  certain  nerve-troubles, — apathy, 
dejection,  inaptitude  for  work,  and  headache,— and  we  generally 
(280) 


HOW   ATJTO-INTOXICATION   IS  PRODUCED.  281 

note  in  the  renal,  cutaneous,  or  pulmonary  excretions  some 
incompletely-oxidized  products  of  disassimilation, — oxalic  acid 
and  the  volatile  fatty  acids.  It  is  admitted,  not  without  an 
appearance  of  reason,  that  these  bodies,  which  are  all  toxic,  are 
not  foreign  to  the  production  of  these  nerve-symptoms.  They 
are  the  very  first  signs  of  poisoning  due  to  the  previous  derange- 
ment of  nutrition.  The  same  injurious  substances,  causing 
similar  nervous  disorders,  may,  in  people  who  are  in  good 
general  health,  be  produced  superabundantly  or  destroyed  insuf- 
ficiently, owing  to  excesses,  late  hours,  mental  anxiet}-,  or  to  the 
influence  of  dampness,  cold,  or  living  in  places  that  are  badly 
ventilated  and  badly  lighted  ;  all  of  which  causes  affect  the  body 
only  by  first  acting  upon  either  the  central  or  peripheral  nervous 
system.  This  is  another  example  of  the  first  signs  of  poisoning 
due  to  a  pathogenic  nerve- reaction.  Amongst  the  substances 
formed  by  certain  microbes  there  are  some  which,  even  in  small 
quantities,  are  eminently  poisonous.  From  such  substances 
certain  microbes  develop  putrefactions,  which  may  become  the 
pathogenic  agents  of  certain  forms  of  septicaemia.  If,  then, 
the  disease  is  not  complicated  by  injury  to  important  organs;  if 
the  microbes  do  not  exist  in  the  blood,  the  nerve-centres,  the 
lungs,  the  liver,  the  kidneys,  or  the  heart ;  if  they  only  exist — sup- 
pose it  is  a  case  of  septicaemia — in  the  cellular  tissue  of  the  region 
contaminated,  it  is  quite  natural  to  attribute  the  general  symp- 
toms to  the  absorption  of  the  poisonous  matter  formed  by  these 
microbes,  and  we  can  hardly  understand  that  these  general 
symptoms  could  have  any  other  origin.  There  are,  then,  to  all 
appearances,  certain  cases  in  which  infection  leads  in  a  secondary 
manner  to  intoxication.  Thus,  man  is  poisoned  not  only  when 
he  swallows  a  poisonous  substance  or  when  he  breathes  :i  im-philic 
gas,  but  also  when  he  is  attacked  by  certain  diseases.  Wh.-n 
the  poison  is  produced  by  some  external  cause,  or  when  it  is 
formed  in  the  system  by  a  perversion  of  the  nutritive  functions 
or  by  the  secretion  of  a  microbe,  it  must  be  considered  an  anom- 
alous substance,  either  as  regards  its  nature  or  its  quantity. 
But  normal  poisons  exist. 

The  healthy  man,  as  I  have  said,  is  both  a  receptacle  and  a 
laboratory  of  poisons.     In  fact,  he  receives  them  in  his  food,  he 


282  LECTURES  ON  AUTO-INTOXICATION. 

creates  them  by  disassirailation,  and  he  forms  them  in  his 
secretions.  The  human  body  is  the  theatre  of  the  toxic  elab- 
orations carried  on  by  the  normal  microbes  which  constantly 
inhabit  the  alimentary  canal.  And  yet  man  is  not  poisoned. 
He  is  defended  in  various  ways  against  poisoning.  In  the  first 
place,  his  liver  protects  him,  by  arresting  on  their  way,  before 
they  pass  into  the  general  circulation,  the  poisons  brought  from 
the  intestine  by  the  portal  vein,  in  order  to  neutralize  them 
or  throw  them  back  into  the  intestine.  Then  the  excretory  sys- 
tem expels  the  poisons  which  are  in  circulation.  This  is  not  a 
purely  theoretical  view.  I  have  demonstrated  it  experimentally, 
taking  the  natural  product  of  an  excretion  and  studying  its 
toxicity  by  injecting  it  into  the  veins  of  an  animal. 

The  traditional  idea  that  normal  urine  is  poisonous  had  been 
rejected  by  Huron;  its  truth  was  only  established  in  1880,  by 
Feltz  and  Ritter.  But  they  only  observed  the  fact  of  the  tox- 
icity of  the  urine ;  they  did  not  pursue  in  detail  the  study  of  the 
characteristics  of  the  poisoning  which  results  from  the  introduc- 
tion of  the  urine  into  the  veins.  I  have  studied  this  subject, 
determining  not  only  the  quality,  but  the  intensity,  of  the  urinary 
toxicity. 

I  found  first  what  mass  of  living  matter  can  be  killed  by  the 
poisons  which  each  kilogramme  of  the  body  of  a  healthy  man 
supplies  in  twenty-four  hours  to  the  renal  secretion.  I  thus 
possessed  a  standard  which  enabled  me  to  study  the  variations 
of  intensity  in  the  urinary  toxicity,  under  certain  physiological 
conditions  and  under  various  pathological  circumstances. 

By  varying  the  experiments  I  showed  that  there  was  not 
one  particular  urinary  poison,  but  that  the  urine  contains  many 
poisons.  Having  by  the  h'elp  of  charcoal  acted  upon  urine  with 
alcohol  so  as  to  separate  its  many  constituents,  I  succeeded 
in  disassociating  the  various  elements  of  its  toxicity,  and  in 
showing  that  it  contains  at  least  seven  toxic  substances:  a 
diuretic  substance  (urea);  a  narcotic  substance;  a  substance 
that  produces  salivation;  one  that  contracts  the  pupil ;  one  that 
lowers  the  temperature;  two  convulsive  substances, — one  of  an 
organic  nature,  the  other  a  mineral  (potass). 

It  is  because  all  these  substances  are  carried  away  through  the 


HOW   AUTO-INTOXICATION   IS   PREVENTED.  283 

urine  that  the  urine  is  poisonous,  and  that  man  escapes.  All 
these  poisons  come  from  the  blood  ;  and  yet  the  blood  is  not 
poisonous,  for  it  is  continually  freeing  itself  from  those  that 
flow  into  it,  either  by  transferring  them  to  the  excretory 
system  or  to  the  various  organs,  or  by  consuming  them  when 
they  are  brought  into  contact  with  the  corpuscles.  I  have  just 
said  that  the  blood  is  not  poisonous  ;  this  assertion  must  not  be 
taken  literally.  As  poisons  are  continually  passing  through  it 
on  their  way  to  the  excretory  system,  the  blood  must  necessarily 
contain  toxic  matter  at  each  moment.  The  blood,  then,  has 
really  a  toxicity,  which  may  be  very  slight ;  the  question  is,  can 
this  degree  of  toxicity  be  disregarded?  To  conclude  that  the 
blood  is  not  poisonous,  from  the  fact  that  man  lives  with  it  dif- 
fused over  all  his  organs,  is  simply  nonsense.  The  only  state- 
ment that  we  can  permit  ourselves  to  make,  a  priori,  is  that 
the  blood  is  not  sufficiently  toxic  for  a  quantity  amounting  to 
1  kilogramme  to  be  able  to  kill  or  even  seriously  injure  13  kilo- 
grammes of  living  matter.  The  toxicity  of  the  blood  is  no 
doubt  considerably  below  this  estimate ;  but  I  have  shown  you 
by  several  experiments  that  this  toxicity  really  exists,  and  I 
have  fixed  the  somewhat  narrow  limits  within  which  it  is  con- 
fined. I  have  been  led  to  the  conclusion  that  a  kilogramme  of 
living  blood  contains  in  its  plasma,  and  only  in  its  plasma, 
enough  poison  to  kill  more  than  1250  grammes  of  living  matter, 
and  that  a  man  would  die  toxsemic  if  his  blood  came  to  con- 
tain ten  times  as  much  poison  as  it  does  in  its  normal  con- 
dition. But  if  the  plasma  of  the  blood  is  only  sligtly  toxic,  its 
cells  contain  poison,  like  all  the  cells  of  the  body,  and  these  toxic 
constituents  of  each  cell  can  only  be  set  at  liberty  by  disassimi- 
lation  or  by  the  destruction  of  the  cell  itself.  Amongst  these 
substances  there  are  some  which  are  toxic.  These  poisons,  which 
are  contained  in  abundance  in  the  cells  of  all  the  tissues,  are 
of  two  kinds ;  there  are  organic  substances  resulting  from  disas- 
simijation  and  secretion,  and  mineral  substances,  at  the  head  of 
which  we  must  place  potass. 

Amongst  the  products  of  secretion,  bile,  which  flows  peri- 
odically into  the  alimentary  canal,  contains  poison  ;  it  derives 
its  toxicity  much  more  from  its  coloring  matter  than  from  the 


284  LECTURES  ON   AUTO-INTOXICATION. 

biliary  salts.  But,  normally,  the  bile  that  is  secreted  is  not  very 
dangerous ;  its  coloring  matter  and  its  salts  are,  for  the  most 
part,  precipitated  in  the  alimentary  canal. 

The  alimentary  canal,  however,  is  an  important  source  of 
poisons ;  it  contains,  in  addition  to  the  potass  supplied  by 
various  foods  and  the  bile,  the  products  of  intestinal  putrefaction. 
I  had  to  take  up  this  question  of  intoxication  by  putrid  products 
from  the  points  of  view  of  many  different  experimentalists, — 
Gaspard,  Panum,  Hemmer,  Bergmann  and  Schmiedeberg,  Ziilzer 
and  Sonnenstein,  Selrni,  Gautier,  Brouardel  and  Boutmy.  Then 
I  studied  intestinal  putrefaction  ;  I  showed  that  alkaloids  exist 
in  faecal  matter,  that  these  alkaloids  are  of  several  kind.s,  and 
that  when  those  of  one  kind  predominate  in  the  intestines  we 
also  find  them  predominate  in  the  urine.  I  established,  accord- 
ing to  Stich,  the  toxic ity  of  faecal  matter.  I  analyzed  the 
elements  of  this  toxicity,  and  showed  that  it  is  due  mainly  to 
potass  and  ammonia,  but  that,  when  freed  from  these  two  ele- 
ments, faecal  matter  still  retains  a  certain  degree  of  toxicity 
which  must  not  be  overlooked.  I  have  shown  that  intestinal 
antiseptic  treatment,  which  causes  the  alkaloids  to  disappear 
from  faecal  matter  and  urine,  diminishes  the  toxicity  of  both. 

Knowing  the  normal  poisons  and  the  various  sources  from 
which  they  spring,  I  was  able  to  study  a  form  of  poison  due  to 
their  retention,  viz.,  uraemia.  But  I  took  care  to  distinguish 
it  from  the  non-poisonous  symptoms  that  arise  in  diseases  of  the 
kidneys, — albumin uria,  haemorrhage,  cardiac  and  arterial  injuries, 
and  oedema,  including  cerebral  oedema.  Thus,  as  you  know,  I 
only  admit  as  ursemic  symptoms  those  that  are  toxic.  I  have, 
moreover,  furnished  the  only  convincing  proof  of  the  reality  of 
toxic  uraemia  by  showing  that  the  urine  of  ursemic  patients  is 
not  poisonous. 

The  urine  of  uraemic  patients  is  not  toxic,  owing  to  the  fact 
that  all  the  poisonous  substances  normally  eliminated  by  the 
urine  are  retained  in  the  system  of  those  suffering  from  this 
disease.  But  is  all  that  is  thus  retained  poisonous  ?  If  only  a 
part  is  poisonous,  which  part  is  it?  It  is  not  urea.  It  is  not 
the  mass  of  extractive  matter  ;  it  is  not  potass  exclusively.  The 
toxicity  cannot  be  explained  by  any  one  of  these  bodies  singly. 


POISONING   OF   THE   INDIVIDUAL  BY   FOOD.  285 

Each  of  them  contributes  a  different  share  to  the  general  tox- 
icity, — the  coloring  matter  three-tenths,  the  extractive  matter 
one-  to  two-  tenths,  and  potass  and  other  mineral  substances 
four-  to  five-  tenths.  The  knowledge  of  the  multiplicity  of  the 
toxic  agents  enables  us  to  understand,  according  to  the  one 
which  predominates,  the  many  clinical  features  that  uraemic 
poisoning  may  assume,  particularly  the  convulsive  and  the 
comatose  forms.  It  explains  the  appearance  of  certain  special 
symptoms,  such  as  low  temperature  and  pupillary  contraction. 

I  think  I  have  succeeded  in  showing  you,  gentlemen,  that 
these  pathogenic  observations  not  only  satisfy  scientific  curiosity, 
but  that  they  have  for  corollaries  practical  applications ;  and 
that,  in  a  word,  they  are  far  from  being  unimportant  from  a 
therapeutic  point  of  view. 

After  having  studied  the  form  of  intoxication  resulting  from 
the  retention  of  the  normal  poisons,  I  commenced  the  study  of 
the  morbid  conditions  caused  by  the  exaggeration  of  their 
formation, — for  example,  gastric  disorders,  constipation,  and 
intestinal  obstruction.  I  traced  the  history  of  various  intoxi- 
cations by  poisons  of  intestinal  origin,  such  as  toxaemia  from 
bad  sausages ;  I  quoted  a  case  of  Senator's,  in  which  the  cause 
of  the  malady  was  hydrosulphuric  acid, — a  case  of  poisoning 
from  fish,  which  I  observed  personally,  and  in  which  the  ill 
effects  were  attributable  to  the  formation  of  an  excessive  quantity 
of  alkaloids ;  I  called  your  attention  to  a  case  of  poisoning 
from  some  preserved  goose,  in  which  Brouardel  and  Boutmy 
discovered  a  poisonous  alkaloid.  I  showed  you  that  all  these 
cases  are,  in  reality,  within  the  domain  of  infection  before  they 
end  in  intoxication.  In  all  these  cases,  in  short,  we  find,  between 
the  consumption  of  the  tainted  food  and  the  appearance  of  toxic 
symptoms,  rather  a  long  period  of  incubation.  It  seems  to  me 
that  the  poison  elaborated  by  the  microbes  in  the  tainted  food 
was  too  small  in  quantity  to  cause  poisoning,  but  that  the 
microbes,  continuing  to  multiply  with  greater  rapidity  in  the 
alimentary  canal,  amounted  in  a  few  hours  to  a  prodigious 
number,  and  that  then  the  toxic  matter  elaborated  by  them 
formed  a  mass  of  sufficient  importance  to  produce  poisoning. 
Here,  again,  incubation  obliges  us  to  admit  infection  ;  but  the 


286  LECTURES  ON    AUTO-INTOXICATION. 

infectious  agents  form  a  poison,  and  the  infection  ends  in 
poisoning.  But  the  most  common  condition  in  which  we  find  in- 
toxication occurring  through  the  excessive  formation  of  poisons 
in  the  alimentary  canal  is,  as  I  have  told  you,  dilatation  of  the 
stomach,  which,  independently  of  the  digestive  and  nervous 
troubles  always  recognized  as  being  attendant  upon  the  various 
forms  of  dyspepsia,  seem  to  me  to  cause  many  other  disorders. 
It  engenders,  especially,  a  habitually  chronic  albuminuria,  which 
may  become  permanent,  but  which  remains  curable  for  a  long 
time,  and  which  is  rapidly  cured  if,  suspecting  its  cause,  we  take 
the  trouble  to  seek  it  out,  and  if,  having  discovered  it,  we  know 
how  to  contend  against  it.  It  is  by  provoking  anomalous  gas- 
tric fermentation,  by  rendering  excessive  intestinal  fermen- 
tation, by  preparing  poisons,  and  especially  acetic  acid,  that 
dilatation  of  the  stomach  vitiates  the  nutrition  of  the  osseous 
tissue  and  produces  a  peculiar  deformity  of  certain  joints, — a 
kind  of  nodose  rheumatism,  osteomalacia,  and,  perhaps,  rachi- 
tis. There  are  other  diseases  of  degeneration  which  spring  from 
disorders  of  the  nutritive  functions  caused  by  dilatation  of 
the  stomach ;  I  will  merely  mention  those  in  which  this  patho- 
genic influence  is  most  manifestly  shown, — chlorosis  and  pulmo- 
nary phthisis. 

I  showed  the  part  played,  even  in  infectious  diseases,  by 
certain  secondary  intoxications,  and  I  was  thus  led  to  expound 
to  you  my  views  as  to  the  treatment  of  typhoid  fever,  the  car- 
dinal points  of  which  are,  in  my  opinion,  intestinal  antiseptic 
treatment,  general  antiseptic  treatment,  antithermic  treatment, — 
consisting  of  tepid  baths,  gradually  cooled, — and  a  certain  sys- 
tem of  dietetics.  I  was  thus  enabled  to  formulate,  with  regard 
to  typhoid  fever,  certain  general  rules  that  might  be  applied  to 
other  acute  diseases. 

I  showed  you  the  share  contributed  by  poisoning  in  jaundice. 
This  poisoning  is  twofold.  The  bile,  contrary  to  what  was  sup- 
posed, is  poisonous  mainly  in  its  coloring  matter.  What  saves 
the  system  from  the  toxic  power  of  this  coloring  matter  is  the 
urine,  which  is  continually  eliminating  a  portion  of  it;  and  also 
the  cellular  tissue  and  the  fibrous  tissues,  the  white  fibres  of 
which  retain  within  themselves  the  excess  of  coloring  matter 


RENAL   ACTIVITY  PREVENTS   AUTO-INTOXICATION.  287 

that  is  not  eliminated,  and  which,  if  it  remained  in  circulation, 
would  seriously  affect  the  working  of  the  nerve-cells.  On  the 
other  hand,  the  biliary  salts  increase  disassimilation,  destroy 
muscle-cells  and  blood-corpuscles,  and  thus  set  free  organic  and 
mineral  poisons,  particularly  potass. 

Now,  in  many  of  the  diseases  that  produce  jaundice  the  liver, 
whose  normal  function  is  to  protect  the  system  against  the  intes- 
tinal poisons,  is  diseased  or  checked  in  its  working.  It  ceases 
to  exercise  its  protective  influence;  it  also  ceases  to  form  urea, 
and  urea  is  the  best  diuretic.  It  is  this  substance  which,  by 
forcing  the  renal  barrier,  carries  away  "the  other  toxic  material. 
Thus,  complete  poisoning  takes  place,  the  successive  phases  of 
which  are  cholaemia,  acholia,  and  uraemia.  In  fact,  in  jaundice, 
the  true  safeguard  against  poisoning  is  the  kidnej'.  As  long  as 
it  acts,  the  patient's  urine  is  very  toxic ;  not  owing  to  the 
bile  which  it  contains,  but  from  the  matter  produced  by  ex- 
aggerated disassimilation.  If  the  kidneys  perform  their  work 
of  depuration  insufficiently,  the  urine  ceases  to  be  toxic,  but 
the  patient  is  poisoned  through  the  retention  of  the  normal 
poisons. 

We  have  seen  that  the  normal  poisons  are  not  alone  the 
cause  of  all  intoxication.  I  showed  you,  in  acute  yellow  atrophy 
of  the  liver,  an  example  of  anomalous  substances  produced  by 
the  vitiated  elaboration  of  matter  by  the  system.  I  allude  to 
certain  unusual  albumens,  to  the  unusual  transformation  of 
medicaments,  such  as  naphthalin,  which  ceases  in  the  case  of 
atrophy  of  the  liver  to  pass  from  the  system  in  the  form  of 
naphthylsulphite  of  soda.  Amongst  these  anomalous  substum-rs 
there  are  some  which  are  toxic. 

I  will  remind  you  that,  in  glycosuric  patients,  besides  the 
symptoms  arising  from  incomplete  destruction  of  the  sugar 
formed  by  the  system,  the  latter  may  generate  a  substance 
which,  in  the  urine  of  patients  attacked  with  diabetic  coma, 
takes  a  claret-colored  tinge  when  brought  into  contact  with  per- 
chloride  of  iron.  This  substance  does  not  exist  only  in  diabetic 
subjects;  it  has  been  found  in  dyspeptic  coma,  in  certain  cases 
of  cancer  of  the  stomach,  pernicious  ansemia,  leucocythffiinia, 
and  I  have  observed  it  in  dilatation  of  the  stomach  and  in 


288  LECTURES  ON   AUTO-INTOXICATION. 

typhoid  fever.  It  has  been  experimentally  established,  as  you 
know,  that  this  substance  is  toxic.  Unlike  the  greater  number 
of  auto-intoxications  that  we  have  met  with  up  to  the  present, 
what  we  call  acetonsemia  is  self-poisoning  by  an  anomalous 
poison, — a  truly  morbid  one. 

In  cholera  an  anomalous  elaboration  of  matter  also  exists,  as 
shown  by  the  violet  coloration  observed,  even  at  the  time  of 
emission,  in  the  urine  of  certain  cholera  patients  that  have  been 
treated  with  naphthalin.  But  cholera  is  an  example  of  complex 
poisoning.  I  told  you  that  there  exists  in  those  attacked  with 
cholera  a  primitive  poison,  the  essence  of  which  is  unknown, 
which  is  produced  either  by  the  system  under  the  influence  of 
pathogenic  microbes,  or  by  these  microbes  themselves.  The 
existence  of  this  poison  is  shown,  in  my  opinion,  by  the  special 
toxicity  of  the  urine  of  cholera  patients,  which,  on  being  injected 
into  rabbits,  produces  in  them  the  choleraic  syndrome, — the 
appearance  of  cholera,  but  not  cholera  itself.  But  I  also  told  you 
that  besides  the  symptoms  caused  by  choleraic  poisoning  those 
suffering  from  cholera  underwent,  at  a  certain  stage  of  the  dis- 
ease, a  secondary  intoxication  through  the  retention  of  the 
normal  poisons,  and  I  indicated  myosis  as  the  clinical  criterion 
of  the  appearance  of  this  uraemic  poisoning. 

I  concluded  the  series  of  these  lectures  with  therapeutic  ap- 
plications, with  regard  to  intoxications  in  general,  deduced  from 
pathogenic  knowledge.  The  treatment  of  self-poisoning  derives 
several  of  its  features  from  the  antiseptic  method.  It  was  nat- 
ural, therefore,  to  see  what  result  might  legitimately  be  expected 
from  general  antiseptic  treatment. 

In  conclusion,  I  gave  you  certain  reasons  and  quoted  certain 
experiments,  of  a  nature  to  lead  us  to  hope  that  in  the  future 
general  antiseptic  treatment  may  produce  good  results. 

And  now,  gentlemen,  having  taken  a  rapid  retrospective 
glance  at  the  ground  we  have  gone  over  together,  I  think  I  am 
justified  in  making  this  assertion  :  When  I  have  hazarded  certain 
hypotheses,  I  have  never  disguised  from  you  the  fact  that  they 
were  hypotheses;  on  the  other  hand,  whenever  I  have  made 
positive  affirmations,  they  have  been  supported  by  experimental 
demonstration. 


INDEX. 


Acetonaemia,  247,  248 
Acetone,  in  urine,  142, 247 

tests  for,  142,  247 
Acholia,  abnormal   metabolism   a  cause 

of,  11 

in  jaundice,  228,  233.  234 
Acid,  acetic,  in  dough,  179 

in  intestine,  16 

in  muscle-extract,  79 

in  putrefactive  products,  16, 93 

in  tissues,  16,  79 

in  urine,  16 

phalangeal  nodes  due  to,  172 
Acid  bile,  140 

Acid,  boracic,  an  antiseptic,  98 
butyric,  in  dough,  179 

in  intestine,  16 

in  muscle-extract,  79 

in  putrefactive  products,  16,  93 

in  tissues,  16,  79 

in  urine,  16 
carbolic,  an  antipyretic,  198,  210,  211 

an  antiseptic,  98.  196 

and  mercury,  196 

in  dough,  179 

in  faeces,  141 

in  intestine,  16,  141,  142 

in  putrefactive  products,  16,  93 

in  tissues,  16 

in  typhoid,  193,  219 

in  urine,  16,  141, 142 

micro-organisms  produce,  12 

toxic  power  of,  196 
cholic,  in  intestine,  18,  223 
cholalic,  in  intestine.  18,  223 
diarrhoea,  139.  140, 168 
dyspepsia,  139,  140 
faeces  of  dilated  stomach.  159 
glycocholic,  in  intestine,  18,  223 
hippuric,  toxic  power  of,  118 

unemia  due  to,  118 

hydrochloric,  an  antiseptic,  88, 149, 158, 
183,  184 

functions  of,  149 

in  dilated  stomach,  183,  184 
lactic,  in  intestine,  16 

in  t  issues,  16 

in  urine,  16 
odor  of  breath.  159 
oxalic,  in  Intestine,  16 

in  tissue,  16 

in  urine,  16 

lira-Una  due  to,  107 

stools.  LM,  iin.  uj 

sulphuric,  micro-organisms  produce,  12 

a  putrefactive  product.  '.'.! 
taurooholio.  in   intestine,  18,  228 
uric,  ride  Uric  acid 
valeric,  in  putrefactive  products,  !»:{ 
vomiting,  139 
Acids,  bile  excretion  of,  227 

fatty,  micro-organisms  produce,  12 

in  dough,  179 

in  intestine,  16,  18,  141, 142,  223 


Acids,  in  muscle-extract,  79 

in  putrefactive  products,  16, 98 

in  tissues,  16 

in  urine,  16, 141, 142 

toxic  power  of,  31,  32 

vegetable,  in  typhoid,  217 
Acne,  in  dilated  stomach,  163 

rosacea,  in  dilated  stomach,  163, 171 
Acquired  diathesis,  7,  8 
Acute  atrophy  of  liver,  circulatory  system 

haemorrhages  in,  232 

jaundice  in,  235 

kidneys  in,  232 

metabolism  in,  232 

naphthalinin.231,232,263 

renal  system  in,  232 

urine  of,  232 
Advantages  of  the  intra-venous  method  of 

study,  24 

Ague,  quinine  in,  198,  209 
Albumen,  and  peptones,  10, 17,  104, 164,  165 

nephritis  due  to,  10 

white  blood-cells  from,  17 
Albuminuria,  exhaustion  due  to,  104 

hydrseiniadue  to.  104 

in  Bright's  disease,  103, 104 

in  diabetes,  246 

in  dilated  stomach,  164, 171.  185 

in  intra-venous  injections,  25,  26,  83, 61, 
73,  87,  248,  264,  266,  267 

in  jaundice,  231 

in  lardaeeous  disease,  104 

in  subcutaneous  injections,  24 

ffidema  in,  105 
Alcohol,  intra-venous  injections  of,  27,  28 

toxic  power  of,  28 

Alcoholic  extract,  intra  \  emm-  injections 
of.  65-57,  77-79,  91,  «6, 142,  148,  267. 

of  blood,  77, 78 

,,1  choleraic  in  inc.  267,  268 

,.:   i 

of  liver,  79 

of  muscle,  79,  112.  148 

of  putrefactive  product*.  9L.M,  MS,  Ml 

of  n line,  .Y.-.-.7.  I..'..  LW,  288 
the  narcolic  of,  56,  125 

the  Bialagoirae  of,  .A  78, 125 

Aleoi.oi, -m.  dilated  -t..inach  due  to.  175 
Alimentary  method  ot  producing  artificial 

toxemia,  23,24 

system,  in  dilated  stomach,  159 

'      in  dx-pcp-i...  I"1'    Hi'.  lUi.  117 
•  •lie  Inline-,  lit..  117 

in  Intestinal  ..i.-nneti..,,.  in 

In    intra  v.  noii*    inji 

66,77 
in  111:1-1111:1.  108,  109 

in  the.  88,  93,  97.101 
in  :i-n,i.i.  r-V  I 
Alkaloid,  sepsii.. 
Alkaloi.K  in  Mood.  i:,.  17.77 

in  faces,  94,  97,  98,  139,  141,  1,50,  262 


(«80) 


290 


Alkaloids,  in  intestine,  97,  98, 155 

in  putrefactive  products,  91-93 

in  tissues,  15,  237 

in  urine,  10,  16,  30,  55,  67,  68,  77,  92,  97, 
98,  125,  141,  150,  155 

intestinal  poisons  due  to,'  139 

micro-organisms  produce,  12 

mydriatic,  92 

of  cholera,  262 

tests  for,  15,  16,  94,  262 

the  total  toxic  power  of,  125 

toxic  power  of,  vide  Toxic  power 

trypsin  develops,  94 
Amaurosis,  in  Bright's  disease,  106 
Ammonaemia,  48, 107,  115-117 

convulsions  in,  116 

temperature  in,  117 
Ammonia,  an  antipyretic,  64,  116, 117 

in  blood,  115 

in  faeces,  96, 139 

in  intestine,  140 

in  putrefactive  products,  93,  96, 140 

in  urine,  115 

micro-organisms  produce,  12 

toxic  power  of,  58,  96,  97,  116, 117, 120 

uraemia  due  to,  107, 115-117 
Anaemia,  pernicious,  odor  of  breath  in, 
167,  247 

urine  of,  142,  247 

urochromes  of,  142 

Angina,  false,  in  dilated  stomach,  161, 171 
Anhidrosis.  in  toxaemia,  151 
Anilin,  antiseptic  power  of, 
:  of,  1! 


of  urine, 


bat 
lim 


toxic  power  of,  196 
Antagonism  of  the  toxic  • 
41-13,  62,  63,  122. 
Antidotes,  in  uraemia,  134,  13 
Antipyretic,  ammonia  as  an,  64,  116,  117 

antipyrin  as  an,  199,  206,  210,  211,  215 

carbolic  as  an,  198,  210,  211 

quinine  as  an,  198.  199,  206,  209-211,  219 

the,  of  urine.  63,  64,  117,  125 

treatment,  205-217 

aths  in,  205,  206,  212-216 
mits  of,  205,  216 
Antiseptics,  anilin,  196 

bile,  88,  93 

boracic  acid,  98 

calomel,  98,  99,  199,  200,  218 

carbolic  acid,  98,  196 

charcoal,  ^98,  100,  136,  174,  184,  191,  192, 

combined,  the  more  effective,  197 
creasote,  98 

formulae  for  use  of,  100,  218,  219 
general,  discussed,  194-199 
hydrochloric  acid,  88,  149,  158,  183,  184 
in  dilated  stomach,  174,  183,  184 
in  typhoid.  Idl-l'i::.  198-200,  218,  219 
intestinal,  98-100,  136,  137,  191-193,  199, 

iodoform,  99,  100,  136,  141,  174,  183,  184, 
193,  199,  218,  219 

,  100,  136,  141,  174,  183,  193, 


potassium  iodide,  196 
sodium  iodide,  196 
toxic  power  of,  99,  196,  197 
uraemia,  136,  137 

Anuria,  choleraic,  78,  112,  271,  272 
enemata  in,  130 
myosis  in,  67,  272 
obstructive,  105,  110,  111,  113 
ocular  symptoms  in,  67,  272. 


Anuria,  treatment  of,  130,  277 

urea  of,  112 

venesection  in,  277 
Aphasia,  in  dilated  stomach,  161 
Arthritic  diathesis,  6-S 
Arthritis  in  dilated  stomach,  165,  166 
Artificial  toxaemia,  methods  of  producing, 

Ascites,  exhaustion  due  to,  104 
Asphyxia,  death  by,  22 

normal  substances  a  cause  of,  10 

toxic  origin  of,  22,  23 
Asthma,  in  dilated  stomach,  164,  171 
Asthmatic  type  in  dilated  stomach,  171 
Ataxia,  dilated  stomach  in,  175 

Bacillus  glutinis.  179 

of  cholera,  252-255,  257,  258,  260,  261, 

268,269 
of  typhoid,  188,  189 

injections  of,  188,  189 
pyocyaneus,  243,  244 

injections  of,  243 

tests  for,  243 

Baths,  in  dilated  stomach,  176, 177 
in  measles,  216 
hi  pneumonia,  216 
in  rheumatism,  216 
in  scarlatina,  216 
in  typhoid,  207,  212-217,  219,  220 
in  uraemia,  128 
inflammations  due  to,  216 
limits  of,  216,  217 
methods  of  use  of,  212-214 
the  results  of,  214-216 
Bile,  acid,  140 

acids,  disease  due  to,  10 

excretion  of,  227 

in  intestine,  18,  223 

amount  secreted  per  diem,  84, 139,  222 
an  antiseptic,  88,  93 
and  urine,  toxic  power  of,  80,  84,  85, 

224 

blood  arrests,  224,  225 
charcoal  acts  on,  81,  135, 136,  224 
composition  of,  222,  223 
excretion  of,  85,  227,  229 
in  urine,  229 

intestinal  toxaemia  due  to.  138,  139 
intra-venous  injections  of,  80,  81,  225, 

liver  arrests,  80,  84,  222-224,  227 

minerals,  toxic  power  of,  82  83,  86 

of  dyspepsia,  140 

pigment,  vide  Bilirubin 

poisons  in,  139 

potass  in,  82,  83,  86 

salts,  tests  for,  225 

toxic  power  of,  81,  224,  227,  229 

suppression  of,  231 

tests  for,  223,  225 

tissues  arrest,  224-227,  229,  230 

total  toxic  power  of,  224 

toxaemia,  222-235 

toxic  power  of,  vide  Toxic  power 
Bilirubin  and  bile-salts,  toxic  power   of, 
224,227 

in  intestine,  223 

intra-venous  injections  of,  224,  226 

properties  of,  223 

tests  for,  223,  225 

tissues  arrest,  225,  227 

toxic  power  of,  vide  Toxic  power 
Blood,  alcoholic  extract  of,  77,  78. 


INDEX. 


291 


Blood,  alkaloids  in  the,  15,  17,  77 

ammonia  in,  115 

amount  of  poisons  in,  necessary  to  pro- 
duce death,  73 

cells,  from  albumen,  17, 165 
destroy  poisons,  17 
liberate  poisons,  78-78 

extract,  iutra-venous  injections  of,  77, 

78 
toxic  power  of,  77,  78 

in  diarrhoea,  104 

indigo  in,  15 

intoxication  of  thet  87 

intra-venous  injections  of,  73, 143 

leucin  in,  231 

micro-organisms  in,  188 

minerals  in,  87 

of  Bright's  disease,  104, 105 

of  cholera,  78 

of  diabetes,  245,  246 

of  jaundice,  230,  231 

of  lardaceous  disease,  104 

of  p>  rexia,  205,  206 

of  typhoid,  188 

of  uraemia,  78,  112,116 

peptones  in,  17,  165 

poisons  in  the,  vide  Poisons 

portal,  15,  17,  72,  143 

potassium  in,  124 

putrefactive  products  in,  88,  89 

sugar  in,  245 

sulphuretted  bydromnte.  15, 149 

the  sialagogue  of,  57,  it,  78 

the  three  sources  of  intoxication  of, 
K7,88 

toxic  power  of,  69-78, 143 

tyrosin  in,  231 

urea  in,  112, 116 

xanthin  in,  2IU 

Bread,  the  fermentation  of.  1<9 
Breath,  odor  of,  in  coma,  Itf7,  247 

in  diabetes,  167,  247,  248 

in  dilat.-.l  stomach,  15!»,  163,  167,  247 

in  dyspepsia.  1-17,  217 

in  l.'-uksi-miii,  I«7.-JI7 

in  pernicious  amuuiia,  167,  .247 

in  tvphoid.  247 
Bright-;  disease,  albuiuinuria  in,  103,  104 

anianrosis  in,  106 

l)l.XKl  of,  101.  111'. 

cerebral  haemorrhage  in,  lOo 
circulatory  system  m,  105,  106 
coma  m.  106 
convulsions  in,  106 
cutaneous  system  in,  lOa 
entorrhagia  in,  105 

C|>M:i\i.-  in.  KIT, 

ha;inateincsis  in,  105 

ha-moriha^o  in.  Ht"),  106 

hyha-mia  m.   I 

inflammation*  in,  106 

nervon.-  -\>tem  in.  106 

ocular  symptom-  in,  108 

cedema  in,  105, 108 

pericarditis  in,  106 

prarico  in,  liio 

puipuni  in.  lu-i 

retinitis  in,  1U6 

symptoms  in,  103-106 
Bronchitis,  in  diluted  stomach.  164,  1<1 
Bulimia,  in  dilated  >tom;irh,  158 
Butyric  acid,  vide  Arid.  l.»t\  i  ic 

Caffeiue,  in  uraemia,  129 


Calomel,  an  antiseptic,  98.  99,  199,  200,  218 

in  typhoid,  200,  201,  218 

disadvantages  of,  200 
Canquoin  paste,  a  caustic,  162 
Carbolic  acid,  vide  Acid,  carbolic 

eneraata  in  typhoid.  193,  219 
Carcinoma,  gastric,  coma  in,  167 

dilated  stomach  due  to,  175 
toxaemia  due  to,  155 
Cardiac  type  of  dilated  stomach,  171 
Cardialgia,  in  dilated  stomach,  159 

in  dyspepsia,  139 

Cerebral  haemorrhage,  in  Bright's  disease, 
105 

oedema,  in  jaundice,  234 

hi  uraemia.  107,  109-111 
Charcoal  acts  on  bile.  81,  135,  136,  224 

on  faeces,  98,  100,  192 

on  putrefactive  products,  92,  136,  141 

on  urine,  54,  57,  98,  100.  125.  192 
Charcoal,  an  antiseptic,  98,  100,  136,  174,  184, 
•  191,  192,  218,  219 

formulae  for  us.-  of.  100,  218,  219 

in  typhoid,  191,  192,  218,  219 

in  uraemia,  136,  137 

Chemistry  of  putrefactive  products.  91,  92 
Chevne-Stokes  respirations,  inchoi. 

in  uraemia,  108 
Chloral,  in  nra-mia,  134 
Chloroform,  in  dilated  stomach,  183,  184 

in  ma-mi.  i.  134 

Chlorosis,  in  dilated  stomach,  158,  172 
Cholaemia.  in  jaundice,  233 

normal  substances  a  cause  of,  10 
Cholalic  acid,  in  intestine,  IN.  '^3 
Cholera,  alkaloids  of,  262 


anuriaof,  78.  111!.  157  1.  '. 
bacillus  of,  252-255,  257, 


- 

258,  280,  281,  388, 


blood  of.  78 

»  In  \  ne-stokes  respirations  in,  271 

etiology  of.  -Jl> 

experimental,  255-259 

la  .,  M  of,  282 
ioilolorm  m.  IN*  i.  "Jill 
mv*i-  in.  I".  1_M.  •-7I.  'jr.' 
naphtlialin  in.  .' 

nervous  svst.-m  in.  i~.  l-'l.  271,  272 
patholo 

renal  system  in,  '-Tl 
respiratory  syst,  m  in.  '.Tl 
sNinpiomsln,  «7.  f.'l.  271,  372 
triiipciatun-  in,  -Tl 
treatment  of.  260,  261 
uraemia  in.  'J71 
nrnif  of,  112,141.268 
Choleraic  urine,  extract*  of  .aW.  9M 
mtra-yeiioiis  Injection  of,  26B  ml 


, 

(  •lio|i--ti-nn,  t..\i,  power  of,  81.  221 
Cli.-lic  aci.l.  i"  intc-tin. 
Circulat..rv  -\~trm.  m  MaM  >eilow  atro- 

phy of  liver 
in  Bright's  disease,  106,  108 

'sie7.2IS.246      , 
in   dilated   stomach,  158,   101,  165,  167, 

171.  172 

in  <l\~]><M>sia,  140 
to  Ifiterfnia  obvtraotiom,  i«4,  1S5 

il.illt.-Mil.kll. 

in  intra-venoua  injectiooa,  38,  86-88,  M, 
in  jau'ii'iUm,1  280,  282,  284,  285 


292 


INDEX. 


Circulatory  system,  in  pyrexia,  203,  204 

in  typhoid,  200 
Clinical  types,  the  ten,  of  dilated  stomach, 

Coma  abnormal  metabolism  a  cause  of,  11 

diabetic,  167,  246-248 

dyspnoea  in,  167 

in  Bright' s  disease,  106 

in  dilated  stomach,  167 

in  dyspepsia,  140, 167 

in  gastric  carcinoma,  167 

in  gastric  ulcer,  167 

in  intra-venous  injections,  32,  47,  55-57, 
77 

in  toxaemia,  140 

in  uraemia,  66, 106,  108 

ligature  of  portal  vein  a  cause  of,  143 

odor  of  breath  in,  167,  247 

pulse  in,  167 

respirations  in,  67,  167 

temperature  in,  108, 167 

the  breath  in,  167 

urine  of,  247 
Constipation,  headache  in,  145 

in  dyspepsia,  146 

in  hypochondriasis,  145 

in  insanity,  145 

migraine  in,  145 

nervous  system  in,  145 

toxaemia  in,  145 

urine  of,  142 

vertigo  in,  145 
Consumptive  type  of  dilated  stomach,  171, 

Convulsions,  and  myosis,  57,  63 
in  ammonaemia,  116 
in  Bright' s  disease,  106 
in  dyspepsia,  140 
in  emaciation,  240 

in  intra-venous  Injections,  34,  37,  38,  51, 
55-57,  74,  77,  79,  86,  87,  93,  95,  233, 
237-240 

in  jaundice,  233 
in  typhoid,  240 
in  uraemia,  66,  106,  108 
Convulsive,  of  urine,  the  inorganic,  64,  65, 

125,239 

the  organic,  62,  63,  65,  125.  239 
potassa,  58,  64,  65,  78,  79,  82,  95, 122,  123, 

urine  of  'jaundice,  82,  86,  87,  233,  238 
of  pyrexia,  123,  238-240 
of  sleep,  37,  41 
Copraemia,  101 

Coryza,  in  dilated  stomach,  164,  171 
Cramps,  in  dyspepsia,  140 

in  intestinal  obstruction,  144 
in  intra-venous  injections,  264,  265 
Creatin,  toxic  power  of,  79,  118 

uraemia  due  to,  118, 119 
Creatinaemia,  117, 128 
Cresol,  in  putrefactive  products,  93 

in  urine,  16, 142 
Cupping,  in  uraemia,  129 
Cutaneous  eruptions,  toxic  origin  of,  162, 

163 

system,  excretion  by,  18-20,  23,  131 
in  Blight's  disease,  105 
in  diabetes,  246 
in  diarrhoea,  139,  168 
in  dilated  stomach,  161-163, 171 
in  dyspepsia,  139,  140.  147 
in  gastric  fullness,  147 
in  gastro-enteritis,  168 


Cutaneous  system,  in  intestinal  obstruc- 
tion, 144, 155 

in  intestinal  toxaemia,  140,  144, 151 
in  intra-venous  injections,  263 
in  jaundice,  230,  235 
in  typhoid,  192,  215 
in  uraemia,  131 
type  of  dilated  stomach,  171 
Jyanosis,  in  intra-venous  injections,  263 

Deafness,  in  dyspepsia,  140 
Death,  amount  of  poison  necessary  to  pro- 
duce, 73 

by  potassium,  123 

by  quinine,  211 

in  infectious  diseases,  236,  237 
Debility,  dilated  stomach  due  to,  175 
Definition,  of  diathesis,  3 

of  uraemia,  96 

of  urotoxic  co-efficient,  35,  47 
Diabetes,  acetonaemia  in,  247,  248 

albuminuria  in,  246 

blood  of,  245,  246 

breath  in.  167,  247,  248 

cataract  in,  246 

circulatory  system  in,  167,  245,  246 

coma  of,  167,  246-248 

cutaneous  system  in,  246 

metabolism  in,  246 

nervous  system  in,  167,  246,  247 

ocular  changes  in,  246 

odor  of  breath  in,  167,  247,  248 

renal  system  in,  245,  247 

respiratory  system  in,  167,  246 

symptoms  in,  167,  246-248 

urea  of,  246 

urine  of,  142,  245-248 

urochromes  of,  142,  247,  248 
Diaphoretics,  in  uraemia,  128 
Diarrhoea,  acid,  139.  140,  168 

erythema  in,  139,  168 

in  dyspepsia,  139,  140 

in  intra-venous  injections,  87,  88,  94, 


in  typhoid, 

in  uraemia,  108, ,  _.. 

nerve-reactions  a  cause  of,  6 

salutary,  19 

toxaemia  due  to,  155 

toxic  power  of  urine  diminished  by,  132 

urine  of,  132,  142 
Diathesis,  acquired,  7,  8 

arthritic,  6-8 

definition  of,  3 

in  dilated  stomach,  165,  166.  169 
Diet,  improper,  dilated  stomach  due  to,  174 

in  dilated  stomach,  177-182 

in  typhoid,  217-219 

in  uraemia,  136,  137 

toxic  power  of  the  urine  varies  with, 

Digitalis,  in  uraemia,  its  dangers  and  uses, 

129,  130 
Disease,  abnormal  metabolism  a  cause  of, 

9-11 

albumens  a  cause  of,  10 
Bright's,  vide  Briglit's  disease 
excess  of  minerals  a  cause  of,  10 

of  water  a  cause  of,  10 
four  pathogenic  processes  in,  2-12 
infectious,  dilated  stomach  a  cause  of, 

176 

dilated  stomach  due  to,  175, 176 
lardaceous,  104 


INDEX. 


293 


Disease  micro-organisms,  a  cause  of,  4,  5, 9 
in  urine  of,  188 

nerve-reactions,  a  cause  of,  2-8,  66, 163 

normal  substances,  a  cause  of,  10, 11 

odor  of  sweat  indicates,  20  • 

pathogenic  processes  in,  2-13 

peptones,  a  cause  of,  10 

secretions,  a  cause  of,  10 

sweat  indicates,  20 

the  causes  of,  must  be  combined,  9 

urochromes  of,  141, 142,  232,  247,  248 
Diseases,  causing  exhaustion,  104 

due  to  abnormal  metabolism,  10,  11 

skin,  in  dilated  stomach,  162,  163 
Diuretic,  the,  of  urine,  60,  61 

urea  as  a,  57,  60,  61,  67,  116,  130,  131,  228, 

231 

Diuretics,  in  uraemia,  129-131 
Dysentery,  a  cause  of  exhaustion,  104 
Dyslysin.  in  intestine,  18,  223 
Dvspcpsia,  acid,  139,  140 

acul  diarrhcea  in,  139,  140 
vomiting  in,  139 

alimentary  system  in,  139, 140, 146,  147 

breath  in,  147,  247 

cardialgia  in,  139 

circulatory  system  in,  140 

coma  in,  140,  167 

constipation  in.  146 

convulsions  in,  140 

cramps  in,  140 

cutaneous  system  in,  139,  140,  147 

deafness  in,  140 

diarrhoea  in,  139,  140 

dilated  stomach  due  to,  161,  174,  175 

erythema  in,  139 

faeces  in,  139, 140 

fatigue  in,  140 

headache  in,  140, 147 

intestinal  antiseptics  in.  111 

intestinal  gases  of,  140, 148, 149 

lavage  in,  147,  148 

nervous  system  in,  140.  147 

ocular  symptoms  in,  140 

paralyses  in.  140 

pyrona  in,  139 

renal  system  in.  140 

secretions  of.  139,  146, 147 

sulphuretted  hydrogen  in,  the  intes- 
tines of.  ]  ill.  1  K.  ]  |(l.  l.V, 

symptoms  of,  139,  140,  HO,  147 

taste  in,  137 

teeth  in,  119 

toxemia  in,  140,  148,  149,  155 

treatment  of,  147,  148 

uni'iiiio  symptoms  in.  140 

u rine  of,  140-142,  l'4»i.  '-M7 

iirorhroiiie-  of,  141,  142,  247 

vertigo  in.  140,  147 

vision  disturbed  in,  140 

vomiting  of,  139 

Dyspeptic  type  of  dilated  stomach,  170 
Dyspnoea,  in  coma,  167 

in  dilated  stomach,  164 

in  uraemia,  67, 108 

Eclampsia,  abnormal  metabolism  a  cause 

of,  11 
Eczema,  in  dilated  stomach,  162,  163, 171 

in  gastro-enteritia,  168 
Emaciation,  convulsion*  in.  240 

in  dilated  Stomach,  165 

in  jaundice,  82,  230 

in  typhoid,  191,  204,  218,  240 


Emetics,  in  uraemia,  131 
Enemata,  in  anuria,  130 

in  dilated  stomach,  182 

in  typhoid,  193,  219 

in  uraemia,  130 
Enteritis,  in  dilated  stomach,  159 

gastro-,  of  children,  168 
Entorrhagia,  in  Bright's  disease.  105 
Epistaxis,  in  Brighfs  disease,  105 

in  jaundice,  230 

in  nerve-reactions,  6 

in  typhoid,  190 
Erysipelas,  in  typhoid,  190 
Erythema,  in  diarrhcea,  139,  168 

in  dilated  stomach,  163 

in  dyspepsia,  139 

in  gastro-enteritis,  168 

in  intestinal  toxaemia,  155 

in  jaundice,  235 
Etiology,  of  cholera,  249-252 

of  dilated  stomach.  169.  174-176 

of  typhoid,  176, 189 

of  uraemia,  109 
Evening,  the  urine  of,  36-40 
Excretion,  of  albumen,  103 

of  bile,  85,  227.  229 

of  bile-acids,  227 

of  fats,  103 

by  the  kidneys,  vide  Kidneys 

of  peptones,  103 

of  poisons,  vide  Poisons 

of  sugar,  103 

of  urea,  71,  103.  116,  204,  207 

of  uric  acid,  103 

of  urine,  103. 125 
Excretory  power  of  kidneys,  103 
Exercise,  urine  of,  43-45 
Exhaustion,  causes  of,  103,  104 
Exophthalmic  goitre,  dilated  stomach  in, 

175 
Exophthalmos,  in  intra-venous  injections, 

33.37.38,74 
Extractives,  in  fa-ces.  111 

in  putrefactive  products,  93 

micro-organisms  produce.  1'J 

toxic  power  of,  1I7-11U.  Iti', 

uremia  due  to,  107, 117-119,  125 
Extracts,  acids  in.  7!> 

alcoholic.  55-37.  77-79,  91,  94-06, 125,  142, 
143.  2«7.  268 

in  typhoid.  "JIT 

intr.i  venous  injections  of,  54 

88.  89.  92-&,  98,  142,  148.  286.  &7\ 

J'.T.  •_'!.•» 

of  blood,  77,  78,  88,  89 

of  choleraic  urine,  387,  388 

,,,• ,.,.,,  .  MI.-*.  H 

of  liver,  78,  TO 

of  nic.it  iii  t\  pboid,  217 

ofm,,s,-]e.7SI7!..88:W,a2.88,H2.143 

of  putrefactive  product*,  88,  80,  91-9* 

.          !378, 125,  267,  268 

the  narcotic,  of  urine,  58, 125 

the  sialogenou*  of  urine.  56,  78, 125 

watery,  64-57.  79,  91-08,  368 

Fasces,  acid,  of  dilated  stomach,  169 
alcoholic  extract  of, 04-08 
alkaloids  in  the,  94,  97,  08,  189, 141,  150, 

ammonia  in.  98,  139 
carbolic  acid  in,  141 
charcoal  acts  on,  98,  100, 192 


294 


INDEX. 


Fasces,  extractives  in,  141 

extracts  of,  94-96,  98 

fetid,  159 

indol  in,  141 

intra-venous  injections  of  extracts  of, 
94,  95,  98 

minerals  in,  139 

naphthalin  acts  on,  99, 100 

of  cholera,  262 

of  dilated  stomach,  159 

of  dyspepsia,  140 

organic  matter  in,  139 

poisons  in.  139,  141 

potass  in,  96, 139 

putrefactive  products  in,  94,  96 

toxic  power  of,  94-96,  98, 139 

watery  extract  of,  94-96 
Fatigue,  in  dyspepsia,  140 
Fats,  excretory  power  of  kidney  for,  103 
Five  modes  of  action  of  microbes,  11,  12 

(1)  anatomical 

(2)  destructive 

(3)  ingestive 

(4)  obstructive 

(5)  productive 

Five  theories  of  uraemia,  107-128 

(1)  ammonaemia,  107,  115-117 

(2)  cerebral  oedema,  107, 109-111 

(3)  extractives,  107,  117-119, 125 
oxalic  acid,  107 
urochromes,  107,  119,  125 

(4)  minerals,  107,  120-126 

(5)  urea,  107,  112,  113 
Flatulence,  in  dilated  stomach,  159 
Food,  intestinal  poisons  due  to,  96,  97, 138 

uraemia  due  to,  126,  136 
Formula  for  use  of  charcoal,  100,  218,  219 

of  iodoform,  100,  218,  219 

of  naphthalin,  100,  218,  219 
Four  pathogenic  processes,  2-13 

(1)  disturbed  nutrition 

(2)  elementary  dystrophies 

(3)  infection 

(4)  nerve-reactions 

Four  sources  of  intestinal  poisons,  138-15? 

(1)  bile 

(2)  faeces 

(3)  food 

(4)  putrefactive  products 
Four  sources  of  toxic  materials,  96 

(1)  food 

(2)  glands 

(3)  putrefactive  products 

(4)  tissues 

Four  sources  of  uraemia,  126, 134-138 

(1 )  disassimilation 

(2)  food 

(3)  putrefactive  products 

(4)  secretions 

Gangrene,  in  typhoid,  190 

Gases,  in  intestine,  19,  140,  148.  149,  155 

Gastric  carcinoma,  coma  in,  167 

dilated  stomach  due  to,  175 
toxaemia  due  to,  155 
urine  of,  142 

catarrh,  dilated  stomach  due  to,  175 
juice  neutralizes  poisons,  88,  93 
ulcer,  dilated  stomach  due  to,  175 
coma  in,  167 
milk  in,  181.  182 
Gastritis,  coma  in,  167 

dilated  stomach  due  to,  175 
in  dilated  stomach,  159 


astro-enteritis  of  children,  symptoms  of, 

168 

lands,  a  toxic  source,  96 
in  jaundice,  230 
in  typhoid,  188 
micro-organisms  in,  188 
Grlycaemia,  10,  245 
GHycerin,  in  typhoid,  218,  219 
intra-venous  injection  of,  28 
toxic  power  of,  28 
Glycocholates,  vide  Bile-salts 
Glycocholic  acid,  in  intestine,  18,  223 
Glycosuria,  245 

Goitre,  exophthalmic,  dilated  stomach  in. 
175 

Hsematemesis,  in  Bright's  disease,  105 
Haematuria,  in  intra-venous  injections,  33, 

51 

laemoglobin,  toxic  power  of,  78 
Haemoglobinaemia,  in  jaundice,  230 
Haemorrhages,  in  acute  yellow  atrophy  of 
liver,  232 

in  Bright's  disease,  105, 106 

in  dilated  stomach,  165 

in  intra-venous  iniections,  33,  51,  73-75 

in  jaundice,  230,  232.  235 

in  nerve-reactions,  6 

in  typhoid,  200 
Headache,  and  constipation,  145 

in  dilated  stomach,  161 

in  uraemia,  108 
Hepatic  type  of  dilated  stomach,  170 
Hernia,  toxaemia  in,  145 
Hippuric  acid,  toxic  power  of,  118 

uraemia  due  to,  118 
Hydatids,  urticaria  a  complication  of,  162, 

163 
Hydraemia.  causes  of,  104 

in  Bright's  disease,  104, 105 

in  jaundice,  234 

in  lavdaceous  disease,  104 

uraemia  due  to,  107,  109-111 
Hydrochloric    acid,    vide    Acid,    hydro- 
chloric 
Hydrogen  sulphide,  in  blood,  15,  149 

in  excretions.  149.  155 

in  intestine,  140,  148, 149,  155 

in  urine,  149 

toxaemia  due  to,  148,  149 
Hydropathic  treatment,  ride  Baths 
Hyperpyrexia,  vide  Fyrexia 
Hypochondriasis,  constipation  in,  14o 

in  dilated  stomach,  171 

Indican,  and  indol,  141 

in  urine,  141,  142 

of  intestinal  disease,  141 
Indigo,  in  portal  blood,  15 
Indol,  and  indican,  141 

in  faeces,  141 

in  intestine,  141 

in  putrefactive  products,  93 

micro-organisms  produce,  12 
Infection,  abnormal  metabolism  precedes, 

and  intoxication,  89-91, 145,  160-153, 186, 

190 

in  typhoid,  189 

nervous  influences  precede,  6,  7 
Infective  disease,  death  in,  236,  237 
dilated  stomach  a  cause  of,  176 
due  to,  175, 176 


INDEX. 


295 


Inhalations,  in  dilated  stomach.  177 

in  uraemia,  128, 135 
Injections,  in  uraemia,  130 

intra-venous,  albuiuinuria  in,  vide  Al 
buminuria 

alimentary  system   in,   vide  Ali- 
mentary system 

circulatory  system  in,  vide  Circu- 
latory system 

coma  in,  vide  Coma 

convulsions  in,  vide  Convulsions 

cramps  in,  264,  265 

exophthalmos  in,  33,  37,  38,  74 

haematuria  in,  33,  51 

haemorrhages  in,  33,  51,  73-75 

morbid  anatomy  in,  88,  89,  143 

myosis  in,  vide  Myosis 

nervous  system  in,  vide  Nervous 
system 

ocular  symptoms  in,  vide  Myosis 
and  Nervous  system 

of  alcohol,  27,  28 

of  alcoholic  extracts,  55-57, 77-79, 91, 
95,  142.  143,  267,  268 

of  bile,  80,  81,  225,  226 

of  blood,  73,  143 

of  blood-extracts.  77,  78 

cf  blue  pus,  243,  244 

of  choleraic  urine,  263-267 

of  diabetic  urine,  24,  25 

of  evening  urine,  36-39 

of  extracts,  vide  Extracts 

of  faecal  extracts,  94,  95,  98 

of  glycerin,  28 

of  jaundiced  urine,  86,  87,  238 

of  liver-extract,  78,  79 

of  micro-organisms,  26, 188,  189,  243, 
244 

of  morning  urine,  36-39 

of  muscle-extracts,  78,  79,  88,  89,  92, 
93,  142, 143 

of  pathological  urines,  24-26,  34.  86, 

of  pus,  243,  244 

of   putrefactive   products,  88,  89, 
91-93,  142, 143 

of  pyrexial  urine,  238,  239 

of  septic  urine,  26 

of  serum,  74-76 

of  sleep,  urine  of,  36-18 

of  soda-lye,  52 

of  tetanic  urine,  237,  238 

of  typhoid  bacillus,  IKS,  189 

of  urea,  49,50,61,  112,  113 

of  uric  acid,  51,  52 

of  urine,  25^59.  86,  87,  237-240,  267, 
268 

of  urochromes,  53 

of  water,  27,  75,  76,  111 

of  watery  extracts,  54-56.  94-96,  268 

reflexes  in,  vide  Reflexes 

renal  system  in,  vide  Kenal  system 

respiratory  system  in,  vide  Respi- 
ratory system 

salivation  in,  vide  Salivation 

temperature  in,  vide  Temperature 

the  strength  of,  28 

urine  in,  264-267 
subcutaneous,  albuminuria  in,  24 

of  urine,  24 

Insanity  and  constipation,  145 
Intestinal  antiseptics,  98-100,  186,  137,  191- 
193,  199.  219 

in  dilated  stomach,  174,  183,  184 


Intestinal  antiseptics,  in  dyspepsia,  141 

in  typhoid,  l!)l-li)3,  '10&-200,  218,  219 

in  uraemia,  136, 137 
disease,  indican  and  indol  of,  141 

urine  of,  141,  142 
fermentation,  symptoms  of,  139 
gases  of  dyspepsia.  140, 148,  149 
obstruction,  circulatory  system  in,  144. 
155 

collapse  in,  144 

cramps  in,  144 

cutaneous  system  in,  144,  146 

earthy  pallor  of,  144 

erythema  in,  155 

lavage  in,  147. 148 

mydriasis  in,  155 

nervous  system  in,  144 

reflex  symptoms  in,  144.  145 

symptoms  of.  144,  145,  155 

sweating  in,  1-14 

toxaemia  due  to,  145, 155 

treatment  of,  147 

tympanites  in,  144 

urine  of,  142 

vomiting  in,  114 
poisons,  origin  of,  138,  138 
toxaemia,  138-192 

acute,  138-153 

anhidrosis  in,  151 

treatment  of,  147, 148 
Intestine,  acetic  acid  in,  16 
acids  in,  16,  18.  141,  142,223 
alkaloids  in,  97,  98, 155 
ammonia  in,  140 
bile-acids  in,  18,  223 

-pigment  in,  223 

-salts  in,  223 
butyric  acid  in,  16 
carbolic  acid  in,  lit,  141,  142 
Cholalir  acid  in.  IS.  223 
cholic  acid  in,  18.  223 
dyslysin  in,  18,  223 
gases  in,  19, 140,  148,  149, 155 
glycocholic  acid  in,  18,  223 
hydrogen  sulphide  in,  140,  148,  148, 155 
indol  in,  141 
lactic  acid  in,  16 
minerals  in,  138,  139 
origin  of  poisons  in,  188, 188 
oxalic  acid  in,  16 
taurocholic  acid  in.  1 
Intoxication,  and  infection,  89-91,  145.  1 .10- 

153,  187, 190 

of  blood,  the  three  sources  of  the.  K7,  K8 
lodoform,  an  antiseptic,  im.im.  !:;«;.  i:;7.  111. 

171.  183,  1*1.  1'.'",.  I!-!..  . 
formulae  for  use  of.  100.  218.  219 
in  cholera,  260,  261 
in  dilated  stomach.  174.  183,  184 
in  typhoid,  193,  218,  219 
in  uramla,  186 

Jaundice,  aeholia  in,  2'J8,  233,  284 
•Ibonlnnrta  in,  231 

bio..d  of.  at".  2:11 

cerebral  0'<lein:i  ill,  i'il 

cholaemia  in,  283 

circulatory  system  in,  230,  232,  234, 285 

convulsions  in,  233 

convulsive  urine  of,  82,  8fi.  87,  238,  288 

cutaneous  system  in,  230,  285 

emaciation  in,  82,  230 

eptotaxta  m.  •..•:;<> 

erythema  in,  235 


296 


INDEX. 


Jaundice,  fatty  degenerations  in,  227,  230 
glands  in,  230 
haemoglobinaemia  in,  230 
haemorrhages  in,  230,  232,  235 
hydraemia  in,  234 

in  acute  yellow  atrophy  of  liver,  235 
in  dilated  stomach,  159, 160, 170 
intra-venous  injection  of  urine  of,  86, 

87,238 

kidneys  in,  227,  228,  230-235 
leucin  in,  231 
liver  in,  228,  230-235 
metabolism  in,  227,  228,  230,  231,  233 
prognosis  of,  233 
pruritus  in,  230 
pulse  in,  230 
purpura  in,  235 
pyrexia  in,  235 

renal  system  in,  227,  228,  230-235 
spleen  'in,  230 
symptoms  in,  225,  230 
temperature  in,  235 
theories  of,  234 
tissues  in,  224-227,  229,  230 
toxaemia  in,  222-235 
toxic  power  of  urine  of,  vide  Toxic 

power 

tyrosinin,231 
uraemia  in,  233-235 
urea  of,  228,  231 
urine  of,  82,  86,  87,  225-227,  229,  231,  233, 

xanthin  in,  231 

Kidneys,  excretion  by  the,  19,  21.  70,  71,  73, 

86, 103,  116,  229,  230,  241,  242 
floating,  160, 164, 170 
in  atrophy  of  liver,  232 
in  dilated  stomach,  160,  164.  172 
in  jaundice,  227,  228,  230,  232,  235 
in  typhoid,  188 
in  uraemia,  106,  108,  131 
micro-organisms  in  the,  188 
vide  Renal  system 

Lactic  acid,  vide  Acid,  lactic 
Lardaceous  disease,  albuminuria  in,  104 

exhaustion  diie  to,  104 

hydraemia  in,  104 

metabolism  in,  104 

peptones  of,  104 

Latent  type  in  dilated  stomach,  170 
Lavage,  in  dilated  stomach,  147, 178, 183, 184 

in  dyspepsia,  147, 148 

in  intestinal  obstruction,  147,  148 

in  toxaemia,  147,  148 
Leeches,  use  of,  in  uraemia,  129 
Leucin,  disease  due  to,  11 

in  blood,  231 

in  dough,  179 

in  muscle-extract,  79 

in  putrefactive  products,  93 

in  tissues,  231 

in  urine,  231 

toxic  power  of,  11,  78,  93,  119 

uraemia  due  to,  119 
Leucocythsemia,  the  breath  in,  167,  247 

urine  of,  142,  238,  247 

urochromes  of,  142,  247 
Leucorrhcea,  exhaustion  due  to,  104 
Liver,  acute  yellow  atrophy  of,  231,  232,  235, 

atrophy  of,  227,  228,  230-234 

bile  arrested,  by,  80,  84,  222-224,  227 


Liver,  enlarged,  ectopia  due  to,  160 

-extract,  intra-venous  injection  of,  78, 

fatty  degeneration  of,  227 

functions  of  the,  230,  231 

in  dilated  stomach,  159,  160,  170 

of  jaundice,  228,  230-235 

poisons  arrested  by,  17,  18,  22,  80,  84, 

142-144,  222-224,  227 

putrefactive  products  arrested  by,  143 
Lungs,  excretion  by  the,  18,  20,  21,  23,  131 

Measles,  baths  in,  216 
Meat,  tainted,  toxaemia  due  to,  151-153 
Meat-extract,  in  typhoid,  217 
Mercury,  advantages  of,  200,  201 

an  antiseptic,  98,  99,  196,  199,  200,  218 

and  carbolic  acid,  196 

disadvantages  of,  200 

in  typhoid,  199-201,  218 

method  of  use  of,  201 

salivation  by,  200 

sequelae  after  use  of,  200 

toxic  power  of,  196 

Metabolism,  abnormal,  acholia  due  to,  11 
coma  due  to,  11 
eclampsia  due  to,  11 
uraemia  due  to,  126, 134,  135 

and  infection,  5 

diminished,  in  uraemia,  135 

in  acute  yellow  atrophy  of  the  liver, 

in  diabetes,  246 

in  iaundice,  227.  228,  230,  231,  233 

in  lardaceous  disease,  104 

in  pyrexia,  204 

in  typhoid,  204 
Micro-organisms,  acid  products  of,  12 

action  of,  on  the  tissues,  11,  12 

alkaloids  a  product  of,  12 

ammonia  a  product  of,  12 

and  peptones,  87 

bacilli,  vide  Bacillus 

carbolic  acid  a  product  of,  12 

extractives  a  product  of,  12 

fatty  acids  a  product  of,  12 

gaseous  products  of,  12 

fn  blood,  188 

in  dough,  179 

in  pus,  vide  Bacillus 

in  the  glands,  188 

in  the  kidneys,  188 

in  the  spleen,  188 

in  the  tissues,  11,  12 

in  the  urine,  188,  243 

indol  a  product  of,  12 

intra-venous  injection  of,  26,  188,  189, 
243, 244      ' 

modes  of  action  of,  11. 12 

of  cholera,  vide  Bacillus 

of  typhoid,  vide  Bacillus 

products  of,  12 

tests  for,  243 

the  five  modes  of  action  of,  11, 12 

the  search  alter,  9 

toxic  products  of,  12 

skatof  a  product  of,  12 

sulphuric  acid  a  product  of,  12 
Migraine,  in  constipation,  145 

in  dilated  stomach,  170 
Milk,  in  dilated  stomach,  180-182 

in  gastric  ulcer,  181,  182 

in  typhoid,  217 

in  uraemia,  130, 135-137 


INDEX. 


297 


Minerals,  as  intestinal  poisons,  138, 139 

disease  due  to  excess  of,  10 

in  bile,  82.  83,  86 

in  blood,  87 

in  faeces,  139 

in  typhoid,  217 

in  urine,  57-59,  64,  65,  82,  83, 116, 117, 120, 
122,  124-126 

table  of  the  toxic  power  of,  124 

total  toxic  power  of,  125,  126 

toxic  power  of,  vide  Toxic  power 

uraemia  due  to,  107,  120-126.  233 
Mixed  urine,  toxic  power  of,  42,  43 
Morbid  anatomy,   in  intra-venous   injec- 
tions, 88,  89, 143 

of  uraemia,  110 
Morning,  the  urine  of,  36-43 

urine,  intra-venous  injection  of,  36-39 
Mortality  of  typhoid,  192, 193,  200,  220,  221 
Muscle,  alcoholic  extracts  of,  79,  142, 143 

and  urine,  the  toxic  powers  of,  93 

-extract,  composition  of,  79 

intra-venous  injection  of,  78,  79,  88, 
89,  92,  93,  142, 143 

putrefactive  products  of,  93 

watery  extract  of,  79,  92, 93 
Mydriasis,  in  intestinal  obstruction,  155 

in  toxaemia,  151 
Mydriatic  alkaloids,  92 
Myosis,  and  convulsions,  57,  63 

in  an u ri:i.  67  272 

in  cholera,  67,  124,  271,  272 

in  intra-venous  injections,  26,  32,  33, 
36-38,  46,  53,  55^57,  74,  79. 86,  87,  93, 
237,  238,  240,  263 

in  uraemia,  67,  124 
Myotic,  the,  of  urine,  63, 125 

Naphthalin,  action  of,  on  faeces,  99, 100 

on  urine,  99,  100 
formula?  for  use  of,  100,  218  219 
in  acute  yellow  atrophy  of  the  liver, 

231,232,263 

in  cholera,  232,  260.  261,  263 
in  dilated  stoniarh.  171.  Ki 
in  typhoid,  litt,  218,  219,  232,  263 
in  uraemia.  136, 137 
in  urine,  99.  100,  232 
Narcotic,  the,  of  urine,  62,  125 

urine,  41,  239 

Nerve-reactions,  a  pathogenic  process,  2-8 
diarrhoea  due  to,  6 
disease  due  to,  2-8,  66, 163 
epistaxis  due  to,  6 
haemorrhages  in,  6 
polyuria  due  to,  6 
syncope  due  to,  6 
-stimulation  in  uraemia,  129 
Nervous  debility,  dilated  stomach  due  to, 

175 
influences  induce  disease,  2-8, 66 

precede  infection,  6, 7 
system,  in  ammonaeraia.  116 
in  anuria,  67,272 
in  Bright's  disease,  106 
in  cholera,  67, 124,  271,  272 
in  constipation,  145 
in  diabetes,  167.  246,  247 
in  dilated  stomach.  161, 167,  170,  171 
in  dyspepsia,  1 10,  1 17 
in  intra-venous  injections,  26,  32-34, 
36-38,  46,  47.  51,  5~3.  S5-57.  74,  77,  79, 
86,  87,  92-95.  233,  237-240,  263 
in  toxaemia,  140, 144, 145,  150, 151, 155 


Nervous  system,  In  uraemia,  66,  67, 106, 108- 

type  of  dilated  stomach,  170,  in 
Neuralgia,  in  dilated  stomach,  161 
Neurasthenia,  dilated  stomach  due  to,  175 
Nodes,  bony,  in  dilated  stomach,  165,  166, 
172,176 

Obstructive  anuria,  105, 110,  111,  113 
Ocular  symptoms,  in  anuria,  67,  272 

in  Bright's  disease,  106 

in  cholera,  67,  124,  271,  272 

in  diabetes,  246 

iu  dilated  stomach,  161 

in  dyspepsia,  140 

in  intra-venous  injections,  vide  Myosis 

in  toxaemia,  151, 155 

in  typhoid,  92 

in  uraemia,  67, 106,  124 
Odor,  of  breath,  vide  Breath 

of  sweat,  in  dilated  stomach,  162 

indicates  disease,  20 
CEdema,  in  Bright's  disease,  105, 106 
Organic,  the,  convulsive  of  urine,  62,63, 65 
Osseous  system,  in  dilated  stomach,  165- 

168, 172,  176,  185 
Osteomalacia,  in  dilated  stomach,  166, 167, 

172 

Oxalic  acid,  vide  Acid,  oxalic 
Oxygen  inhalations,  in  dilated  stomach, 

in  uraemia,  135 

Paralyses,  in  dilated  stomach,  161 

in  toxaemia,  151 
Peptones,  and  albumen,  10. 17, 104, 164, 165 

and  micro-organisms,  87 

blood-cells  transform,  17,  165 

disease  due  to,  10 

excretion  of,  103 

in  dilated  stomach.  182 

in  the  urine.  164,  165 

in  typhoid,  217-219 

of  lardaceous  disease,  104 

toxic  power  of.  10 

Percussion  sign,  in  dilated  stomach,  156 
Pericarditis,  in  Bright's  disease,  106 
Phalungeal  nodes,  in  dilated  stomach,  165, 

166,  172,  178 

P  ..ebitis,  in  dilated  stomach,  165,  171 
Phthisis,  in  dilated  stomach.  1 
Physical  signs  of  dilated  stomach.  1.56-158 
Pityriasis  versicolor,  in  dilated  stomach, 

162 
Pneumonia,  baths  in,  216 

quinine  in,  198 
Poison,  uraemia  is  a  complex,  109, 127,  128, 

Poisons,  amount  of,  necessary  to  produce 

death,  78 
blood  a  source  of,  77,  78 

arrests.  17  224  225 
excretion  of,  15, 18,  20-23,  66,  70-78, 102, 

103 
food  a  source  of,  98,  97, 138 


gastric  juice  neutralizes,  88,  W 
hi  blood,  is.  17.  70-73,  bsTw 
in  faeces.  139, 141 
in  the  alimentary  system, 
in  tissues.  16.  22,  83,  98,  97, 
in  urine.  16.  141,  142 
liver  arrests,  vide  Liver 
modes  of  arrest  of,  144 
origin  of,  98,  87 


87.  101 


298 


INi)EX. 


Poisons,  purgatives  remove,  132 

putrefactive  products  a  source  of,  88- 

90, 138, 139 

Portal  blood,  15, 17,  72, 143 
indigo  in,  15 

sulphuretted  hydrogen  in,  15 
toxic  power  of,  72, 143 

vein,  coma  after  ligature  of,  143 
Potassium,  action  of,  as  a  toxic  power, 
122,123 

an  antiseptic,  196 

as  a  convulsive,  vide  Convulsive 

bromide,  dangers  of,  134 

chloride,  toxic  power  of,  122, 124 

death  by,  123 

in  bile,  82,  83,  86 

in  blood,  124 

symptoms  due  to,  123 

total  toxic  power  of,  125, 126 

toxic  power  of,  vide  Toxic  power 

uraemia  due  to,  107, 120-126,  233 
Prognosis,  of  dilated  stomach,  185 

of  jaundice,  233 
Pruritus,  in  jaundice,  230 
Ptisan,  in  typhoid,  217 
Puerperal  fever,  quinine  in,  198,  210 
Pupil,  vide  Mydriasis  and  Myosis 
Purgatives,  in  surgical  operations,  148 

in  typhoid,  193,  218 

in  uraemia,  131, 132. 135 

remove  poisons,  132 
Purpura,  in  Bright's  disease,  105 

in  dilated  stomach,  165 

in  jaundice,  235 
Putrefactive  products,  alkaloids  in,  91-93 

ammonia  in,  93,  96, 140 

and  urine,  93 

a  source  of  poisons,  88-90. 138. 139 

charcoal  acts  on,  92, 136, 141 

composition  of,  93 

extracts  of,  88,  89,  91-93,  96, 142, 143 

in  blood,  88,  89 

in  faeces,  94, 96 

intra-venous  injection  of,  88,  89,  91-93, 
142, 143 

liver  arrests,  143 

toxaemia  due  to,  139-141, 145, 149-153 

toxic  power  of,  vide  Toxic  power 
principles  in.  93 

trypsin  develops.  94 

uraemia  due  to,  126, 134-136,  233 
Pylorus,  obstructed,  dilated  stomach  due 

to,  175 
Pyrexia,  artificial,  203 

baths  in,  206,  207,  212-217,  220 

blood  of,  205,  206 

circulatory  system  in,  203,  204 

convulsive  urine  of,  vide  Convulsive 

diet  in,  217-219 

discussed,  202-209 

effects  of.  202,  203 

heart  in,  204 

in  jaundice,  235 

in  typhoid,  191 

metabolism  in,  204 

multiple  causes  of.  205,  207-209 

pathology  of.  205.  200,  208,  209 

quinine  in,  198,  199,  206.  209-211,  219 

salutary,  202 

treatment  of,  205-207.  209-217 

urine  of,  vide  Convulsive 

urochromes  of,  240 

venesection  in,  205 

veratrin  in,  205 


an  intermittent  remedy,  210 
death  due  to,  211 
in  ague,  198,  209 
in  pneumonia,  198 
in  puerperal  fever,  198,  210 
in  pyrexia,  vide  Pyrexia 
in  typhoid,  198,  199,  206,  207,  210,  211,  219 
limits  of,  198,  206.  209 
method  of  use  of,  210 

Recapitulation,  general,  280-288 
Reflex  symptoms,  in  toxaemia,  144,  145 
Reflexes,  in  intra-venous  injections,  26,  33, 

36-38,  47,  74 

Renal  system,  in  acute  yellow  atrophy,  232 
in  cholera,  271 
in  diabetes,  245,  247 
in  dilated  stomach,  160, 164, 165, 171, 

185 

in  dyspepsia,  140 

in  intra-venous  injections,  25,  26, 
32,  33,  36,  47,  55,  56,  87,  243.  264, 
266,267 

in  jaundice,  227,  228,  230-235 
vide  Albuminuria  and  Kidneys 
type  of  dilated  stomach,  171 
Respiratory  system,  in  cholera,  271 
in  coma,  67, 167 
in  diabetes,  167,  247 

in  dilated  stomach,  158, 163, 164,  167, 172 
in  intra-venous  injections,  26,  36,  37, 46, 

50,  74,  86,  89,  93 
in  typhoid,  190,  200 
in  uraemia,  66,  106, 108. 131 
Revulsives,  in  uraemia,  129 
Rheumatic  type  of  dilated  stomach,  171 
Rheumatism,  baths  in,  216 
Rickets,  in  dilated  stomach,  166, 168, 172 

Salivation,  in  intra-venous  injections,  47, 
55-57,  77,  79, 125 

in  uraemia,  67 

mercurial,  200 
Sausages,  toxaemia  due  to,  151-153 
Scarlatina,  baths  in,  216 
Secretions,  uraemia  due  to,  126, 134-136 
Sepsine,  an  alkaloid,  91 
Septic  urine,  intra-venous  injection  of,  26 
Serum,  intra-venous  injection  of,  74-76 
Seven,  the.  toxic  principles  of  urine,  60-65 

(1)  antipyretic 

(2)  convulsive,  inorganic 

(3)  convulsive,  organic 

(4)  diuretic 

(5)  myotic 

(6)  narcotic 


ogueth     of  blood.  57,  77,  78 
the,  of  urine,  56,  57,  62,  125 

Sinapisms,  in  uraemia,  129 

Skatol,  in  putrefactive  products,  93 
in  urine,  12 
micro-organisms  produce,  12 

Skin,  vide  Cutaneous  system 

Sleep,  the  urine  of,  36-43 

Soda,  an  antiseptic,  196 
in  the  urine,  67 

-lye,  intra-venous  injection  of,  52 
toxic  power  of,  vide  Toxic  power 

Spleen,  the,  vide  Glands 

Stercorsemia,  101 

Stomach,  dilated,  acid  faeces  of,  159 
acne  in,  163, 171 
albuminuria  in,  164, 171, 185 


INDEX. 


Stomach,  dilated,  alcoholism  a  cause  of, 

175 

alimentary  system  in,  159 
and  typhoid,  176,  186 
angina,  false,  in,  161,  171 
antiseptics  in,  174,  183, 184 
aphasia  in,  161 
arthritis  in,  165.  166 
asthma  in,  164, 171 
asthmatic,  type  of,  167 
baths  in,  176,  177 
bread  in,  178,  179 
bronchitis  in,  164, 171 
bulimia  in,  159 
carcinoma  a  cause  of,  175 
cardiac  type  of,  171 
cardialgiain,159,  171 
chlorosis  in,  158,  172 
circulatory  system  in,  158,  161,  165, 

167, 171, 172 

clinical  types  of,  170-172 
coma  in,  167 

consumptive  type  of.  171,  172 
contractions  in,  161,  171 
coryza  in,  164,  171 
cutaneous  system  in.  161-163, 171 
cutaneous  type  of,  171 
debility  a  cause  of,  175 
diathesis  in,  165, 166,  169 
diet  in,  177-182 

dyspepsia  a  cause  of,  161, 174, 175 
dyspeptic  type  of,  170 
dyspnoea  in.  164,  167 
eczema  in,  162,  163,  171 
emaciation  in,  165 
enemata  in,  182 
enteritis  in,  159 
erythema  in,  163 
etiology  of.  169,  174-176 
faeces  of,  159 
fluids  in,  178,  180,  181 
gastric  causes  of,  175 

Gastritis  in.  159 
aemorrhages  in,  165 
headache  in,  161 
hemiopia  in,  161 
hepatic  type  of,  170 
heredity  in.  169,  175 
hydrochloric  acid  in   183,  184 
hypochondriasis  in,  171 
improper  diet  a  cause  of,  174 
in  ataxia,  175 
in  goitre,  175 
infectious  disease  a  cause  of,  175, 

I7i; 

infectious  disease  due  to,  176 
inhalations  in,  177 
jaundice  in,  ir.il.  HiO,  170 
kidneys  in,  160.  \M,  170 
latent  type  of.  170 
lavage  in,  147,  178,  183,  184 
litniasis  in,  170 
liver  in,  159, 160,  170 
mental  causes  of,  175 
migraine  in,  170 
milk  in,  180-182 
nervous  causes  of,  175 
nervous    system    in,   161.    107,   170, 

171 

nervous  type  of.  170,  171 
neuralgia  in,  161 
night-sweats  in.  Hit 
nodes,  bony,  in.  UB,  166.  172,  176 
ocular  affections  in,  161 


Stomach,  dilated,  osseous  system  in,  165- 

168,  172,  176,  185 
osteomalacia  in.  166, 167,  172 
paralyses  in,  161 
peptones  in,  182 
percussion  sign  in,  156 
phlebitis  in,  165, 171 
phthisis  in,  158, 172 
physical  signs  of,  156-158 
pityriasis  versicolor  in,  162 
prognosis  of,  185 
purpura  in,  165 

renal  system  in,  l(K),  164,  165, 171,  185 
respiratory  system  in,  158,  163,  164, 

167,  172 

rheumatic  type  of,  171 
rickets  in,  166,  168,  172 
splashing  sign  in,  157, 158 
stimulants  in,  178, 181 
succussion  sign  in,  156 
symptoms  of,  158-172 
the  breath  in,  159,  163, 167,  247 
the  sweat  of,  162 
the  ten  clinical  tvpes  of,  170-172 
toxaemia  in,  155-m 
treatment  of,  174-186 
urine  of,  142,  164, 165,  171,  247 
urochrouies  of.  142. 165.  247 
urticaria  in,  162,  163, 171 
vertigo  in,  161 

Succussion  sign,  in  dilated  stomach,  156 
Sulphuretted   hydrogen,  vide  Hydrogen 

sulphide 

Sulphuric  acid,  vide  Acid,  sulphuric 
Summary  of  the  treatment  of  typhoid, 

218-220 

of  uraemia,  137 
Sweat,  vide  Odor  of 
Symptoms,  in  anuria,  67,  272 
in  Bright's  disease,  103-108 
in  jaundice,  225,  230 
in  potass  poisoning,  123 
in  toxaemia,  150,  151 
in  typhoid,  1!M),  191,  200 
in  uraemia,  66,  67,  106.  108,  109 
of  aimnoiwmia,  llli.  117 
of  dilated  stomach.  158-172 
of  dyspepsia,  139-147 
of  gastro-enteritis,  168 
of  intestinal  obstruction,  144,  145,  155 

Table  of  the  toxic  power  of  minerals,  124 
Taurocholic  acid,  in  intestine,  18,  223 
Teeth,  changes  in  the,  in  dyspepsia,  139 
Temperature,  in  ammonaMnia,  117 
in  cholera.  'J71 
in  coma,  108,  167 

in  intra  venous  injections,  25,  26,  38, 
86-38.  47,  49,  58,  55-57,  238,  240,  243, 
264.  265 

in  uraemia,  67,  108,  135 
vide  Pyrexia 
Ten,  the,  clinical  types  of  dilated  stomach, 

170-172 

(1)  asthmatic 
('_')  cardiac 
(3)  consumptive 

I  1  I   cutaneous 

(5)  dyspeptic 

(6)  hepatic 

(7)  latent 

(8)  nervous 

(9)  renal 

(10)  rheumatismal 


300 

Tests,  for  acetone,  142,  247 
for  alkaloids,  15,  16,  94,  262 


INDEX. 


,     ,     ,     , 

for  bacillus  pyocyaneus,  243 
225 


toxication    of 


for  bile,  223, 

Tetanus,  the  urine  of,  237,  2:38 
Therapeutics,  general,  273-279 
Three,    the,   sources   of 
blood,  87,  88 

(1)  bile 

(2)  minerals 

(3)  putrefactive  products 
Tissues,  a  toxic  source,  96 

acids  in,  16,  79 
alkaloids  in,  15,  237 
bile  arrested  by  the,  224-227,  229,  230 
in  jaundice,  224-227,  229,  230 
in  uraemia,  112 
leucin  in,  231 

micro-organisms  in  the,  11,  12 
poisons  in,  vide  Poisons 
urea  in  the,  112 

Toxaemia,  acute  intestinal,  138-153 
auhidrosis  in,  151 
bile,  138,  139,  222-235 
chronic  intestinal,  155-186 
constipation  a  cause  of,  145 
cutaneous  system  in,  140,  144,  151,  155 
diarrhoea  a  cause  of,  155 
etiology  of,  145,  155 
food  a  source  of,  96,  97,  138 
four  sources  of,  96,  138-153 
hydrogen  sulphide  a  cause  of,  148,  149 
in  dilated  stomach,  155-172 
in  dyspepsia,  vide  Dyspepsia 
in  hernia,  145 
in  jaundice,  222-235 
in  typhoid,  190 

methods  of  producing  artificial,  23,  24 
nervous  system  in,  vide  Nervous  sys- 

tem 

ocular  symptoms  in,  151,  155 
paralyses  in,  151 
putrefactive  products  a  source  of,  vide 

Putrefactive  products 
symptoms  in,  148-151 
tainted  food  a  cause  of,  149-153 
treatment  of,  147,  148 
urine  of,  140-142 
urochromes  of,  142 
vertigo  in?  150 
vomiting  in,  150 

Toxic  accidents,  why  infrequent,  17 
coefficient,  35,  47 
materials,  96,  138-153 
origin  of  cutaneous  disease,  162,  163 
Toxic  power,  of  acid  urine,  31,  32 
of  alcohol,  28 
of  alkaloids,  10,  14,  15,  18,  30.  54,  56,  58. 

62,  67,  68,  77,  91-94,  125,  139,  151. 

237,  239 

of  ammonia,  58,  96.  97,  llfi,  117,  120 
of  anilin,  1% 
of  antiseptics,  99,  196,  197 
of  aromatics  of  urine,  53 
of  bile,  15,  18,  80-82,  84-S6,  96,  97,  119,  135, 

139,2241235 

and  urine,  80  84,  85,  224 
of  bilirubin,  81,  119,  135,  139,  224,  229 
of  blood  69-78,  143 
of  carbolic  acid,  196 
of  cholesterin,  81,  222 
of  creatin,  79,  118 
of  extractives.  117-119,  125 
of  faeces,  94-96,  " 


["oxic  power,  of  glycerin,  28 
of  haemoglobin,  78 
of  hippuric  acid,  118 
of  jaundiced  urine,  82,  86,  87,  229,  233, 

of  leucin,  11,  78,  93,  119 
of  leukaemic  urine,  238 
of  mercury,  196 

of  minerals,  10,  15,  18,  43,  48,  53,  54,  57, 
58,  61,  64,  65.  77-79,  82,  83,  86,  95-97, 
120-126,  134,  138,  139.  196.  233,  240 
of  pathological  urines,  34,  237-241 
of  peptones,  10 
of  pigments,  vide  Toxic  power  of  bili- 

rubin  and  urochromes 
of  potassium,  vide  Toxic  power  of  min- 
erals 

of  pus,  243 
of  putrefactive  products,  87-93,  97,  139- 

141,  150-153 

of  pyrexial  urine,  123,  238-240 
of  secretions,  10, 15 
of  serum,  74-76 
of  soda,  57,  58,  61,  67,  121,  134 
of  sugar,  245 
of  tainted  meats,  149-153 
of  typhoid  urine,  92,  192,  238 
of  tyrosin,  119 
of  urea.  48-50,  57,  60,  61,  67, 107,  112-114, 

126 

of  uric  acid,  51,  52,  118 
of  urine,  and  bile,  80,  84,  85,  224 

concentrated,  34,  48 

decolorized,  86,  87 

mixed,  42,  43 

of  evening.  36-40 

of  exercise,  43-45 

of  diarrhoea,  132 

of  jaundice,  82,  86,  87,  229,  233,  238 

of  leukaemia,  238 


of  morning,  36-43 

of  pvrexia,  123,  238-240 

of  sleep,  36-43 


of  typhoid,  92,  192,  238 

of  uraemia,  111,  112.  114,  238 

pathological,  34,  237-241 

the  total,  125,  126 

variations  in  the,  34-46,  48 
of  urochromes,  10,  11,  53,  119,  120,  125, 

240 

of  water,  10.  48,  75 
of  xanthin,  119 
the  total,  of  alkaloids,  125 

of  bile,  224 

of  extractives,  125 

of  minerals,  121,  125,126 

of  pigments,  119,  120,  125 

of  urea,  120 

of  urine.  125,  126 
Toxic  powers,  table  of  the,  124 

of  urine,  antagonism  of  the,  62,  63,  122, 
123 


origin  of  the.  69 
ratio  o 


of  the.  120 

the  seven,  60-65 

Treatment,  antipyretic,  vide  Antipyretic 
antiseptic,  vide  Antiseptic 
hydropathic,  vide  Baths 
of  amiria,  130,  277 
of  cholera,  260,  261 
of  dilated  stomach,  174-186 
of  dyspepsia,  147,  148 
of  measles,  216 
of  pneumonia,  207,  216 


301 


Treatment,  of  puerperal  fever,  198,  210 

of  rheumatism,  216 

of  scarlatina,  216 

of  typhoid,  191-220 

of  uraemia,  128-137 
Trypsin  develops  alkaloids,  94 
Typhoid,  anaemia  in,  200 

and  dilated  stomach,  176,  186 

baths  in,  vide  Baths 

blood  of,  188 

calomel  in,  200,  201,  218 

carbolic  acid  in,  193,  219 

charcoal  in,  191,  192.  218,  219 

circulatory  system  in.  200 

complications  of,  190,  200 

convulsions  in,  240 

cutaneous  system  in,  192,  215 

diarrhoea  in,  189 

diet  in,  217-219 

emaciation  in,  191,  204,  218,  240 

endocarditis  in,  200 

enemata  in,  193,  219 

erysipelas  in.  190 

etiology  of,  176,  189 

glycerin  in,  218,  219 

haemorrhages  in,  200 

inoculation  of,  188.  189 

iodoform  in,  vide  lodoform 

metabolism  in,  204 

micro-organisms  of,  188,  189 

milk  in.  217 

minerals  in,  217 

mortality  of,  192,  193,  200,  220,  221 

naphthalin  in,  vide  Naphthalin 

ocular  symptoms  in,  92 

peptones  in,  217-219 

ptfean  in,  217 

purgatives  in,  193,  218 

pyrexia  in,  191 

quinine  in,  vide  Quinine 

respiratory  system  in,  190,200 

sequelae  of,  200 

summary  of  treatment  of,  218-220 

symptoms  in,  ](*>.  191,  200 

the  bacillus  of.  188,  189 

the  breath  in,  247 

the  glands  in,  188 

toxaemia  in.  I:MI 

treatment  of,  191-220 

urea  of.  204 

urine  of,  92,  141,  142,  188,  192,  238,  247 

urochromes  of,  142,  247 

vegetable  acids  in,  217 
Tvrosin.  in  blood,  2:11 

in  dough.  17!i 

in  muscle-extract,  79 

in  putrefactive  products,  93 

in  uraemia.  119 

in  urine,  231 

toxic  power  of,  119 

Uraemia,  a  complex  poison,  109,  127,  128, 


. 
abnormal  metabolism  :\  cause  of,  126, 

i  :i.  l.r, 
alimentary  system  in,  108,  109,  126,  134, 

ammonia  a  cause  of,  107,  115-117 

antidotes  in.  131.  13."i 

antiseptics  in.  i::«i,  1  •:' 

baths  m,  128 

1.1  .....  1  of.  78.  112,  116 

bromides  in  ;  their  dangers,  134 

caffeine  in,  129 


Uraemia,  cerebral  oedema  a  cause  of,  107, 

charcoal  in,  136, 137 

chloral  in,  134 

chloroform  in,  134 

coma  in,  66, 106,  108 

convulsions  in,  66.  106, 108 

creatin  a  cause  of,  118,  119 

cutaneous  system  in,  131 

definition  of,  96 

diarrhoea  in,  108, 132, 133 

diet  in,  136, 137 

digitalis  in,  129,  130 

diminished  metabolism  in,  135 

diuretics  in,  129-131 

dyspnoea  in,  67, 108 

emetics  in,  131 

enemata  in,  130 

etiology  of,  109 

extractives  a  cause  of,   107,   117-119, 

food  a  source  of,  126, 136 

four  sources  of.  126,  134-138 

headache  in,  108 

hippuric  acid  a  cause  of.  1J8 

hyursemia  a  cause  of,  107, 109-111 

in  jaundice,  233-235 

inhalations  in,  128,  135 

injections  in.  130 

iodoform  in,  136 

kidneys  in.  106,  108.  131 

leucin  a  cause  of,  119 

milk  in,  130,  135-137 

minerals  a  cause  of,  vide  Minerals 

morbid  anatomy  of,  110 

myosis  in,  67, 123 

naphthalin  in,  136,  137 

nerve-stimulation  in,  129 

nervous  system  in,  66,  67, 106, 108-110 

obstructive,  110,  111,  113 

ocular  symptoms  in,  67,  106,  124 

of  cholera.  271 

oxalic  acid  a  cause  of,  107 

pathology  of.  107-128 

potass  a  eau-e  ui.  !•/(/<•  Minerals 

purgatives  in,  131.  1 

putrefactive,  products  a  cause  of,  126, 

184-188,$ 

respiratory  system  in,  66,  106,  108, 131 
revulsives  in,  129 
salivation  in,  67 

secretions  a  source  of,  12t>,  134-136 
summary  of  the  treatment  of.  137 
symptoms  m,  (Hi.  1-7.  KKi.  10K,  100 
the  five  theories  of,  107-128 
treatment  of.  12S-137 
tvroMii  a  cau-c  of.  lift 
urea  a  cau-e  ..f,  lnT,  112.  113 
urea  in,  130,  131 

uric  acid  a  cail-e  of.  MX 

urine  of.  M.  ii7.  Ins,   nut,  ni,  112,  114, 

uroehromes  a  cause  of,  107,  119,  125 

\cne-i-ction  in.  133 

vicarious  fum-iion-  in,  I'M 

vomiting  in.  li-s.  |::i 

when  does  it  occur  ?  108 
Uraemic  symptoms,  in  dyspepsia,  140 

in  eXOMUTfl  vomiting.  111) 
l"iea.  a  diuretic,  rir/r  iMurctic 
iction  of,  vide  Excretion 

in  blood.  112.  116 

in  the  tame*.  ii-J 

in  uremia,  130, 131 


302 


Urea,  intra-venous  injection  of,  vide  In- 
jection 

of  anuria,  112 

of  diabetes,  246 

of  jaundice,  228,  231 

of  typhoid,  204 

toxic  power  of,  vide  Toxic  power 

urzemia  due  to,  107,  112,  113 
Uric  acid,  excretion  of,  103 

intra-  venous  injection  of,  51,  52 

toxic  power  of,  51,  52,  118 

uraemia  due  to,  118 
Uricaemia,  10 
Urine,  acetic  acid  in,  16 

acetone  in,  142,  247 

acids  in,  16,  141,  142 

albumen  in,  vide  Albuminuria 

alcoholic  extract  of,  55-57,  125,  267,  268 

alkaloids  in,  vide  Alkaloids 

ammonia  in,  115 

and  bile,  toxic  power  of,  80,  84,  85,  224 

and  putrefactive  products,  93 

antagonism  of   the  toxic  powers  of, 
41-43,  62,  63,  122,  123,  239 

aromatics  of,  53 

butyric  acid  in,  16 

carbolic  acid  in,  16,  141,  142 

charcoal  acts  on  the,  54,  57,  98,  100,  125, 

concentrated,  toxic  power  of,  34,  48 

convulsive,  vide  Convulsive 

cresol  in,  16,  142 

decolorized,  toxic  power  of,  86,  87 

diabetic,  142,  245-248 

excretion  of,  103,  125 

extractives  of,  uraemia  due  to,  107,  117- 

119,  125 

extracts  of,  54-57,  78,  125,  267,  268 
hydrogen  sulphide  in,  149 
in  diarrhoea,  132,  141,  142 
indican  in,  141,  142 
intra-venous  injections  of,  vide  Injec- 

tions 

lactic  acid  in,  16 
leucin  in,  231 

micro-organisms  in  the,  188,  243 
minerals,  their  toxic  power,  vide  Min- 

erals and  Toxic  power 
mixed,  toxic  power  of,  42.  43 
naphthalin  acts  on  the,  99,  10 
normal,  toxic  power  of,  30 
of  acute  yellow  atrophy  of  liver,  232 
of  anaemia,  142.  247 
of  cholera,  112,  141,263 
of  constipation,  142 
of  day,  and  sleep,  41 

is  narcotic,  41 

of  dilated  stomach.  142,  164,  165,  171,  247 
of  dyspepsia.  140-142,  246,  247 
of  evening,  36-40 
of  exercise,  43-45 
of  intestinal  disease,  141,  142 

obstruction,  142 

ndice 
e,  104 

of  leukaemia.  142,  238,  247 
of  morning.  36-43 
of  nerve-reactions,  6 
of  pyrexia,  vide  Convulsive 
of  sleep  and  day,  36-43 

toxic  power  of,  36-43 
of  tetanus,  237,  238 
of  toxaemia,  140-142 
Of  typhoid,  92,  141,  142,  188,  192,  238,  247 


ostructon,  142 
of  jaundice,  vide  Jaun 
of  lardaceous  disease, 


Urine,  of  uraemia,  66,  67,  108,  109,  111,  112, 
114,  115,  238 

origin  of  the  toxic  powers  of,  69 

oxalic  acid  in  the,  16 

pathological,  34,  237-241 

peptones  in,  164.  165 

poisons  in,  16, 141,  142 

purgatives  diminish  toxic  power,  132 

septic,  injections  of,  26 

skatol  in,  12.  16 

soda  in,  toxic  power  of,  vide  Toxic 
power  of  soda 

subcutaneous  injection  of,  25 

sugar  in  the,  245 

the  antipyretic  of,  63,  64, 117, 125 

the  diuretic  of,  60,  61 

the  narcotic  of,  62, 125 

the  seven  toxic  principles  of,  60-65 

the  sialagogue  of,  56,  57,  62,  125 

total  toxic  power  of,  125, 126 

toxic  power  of,  vide  Toxic  power 
principles  in,  the  seven,  60-65 

ty rosin  in,  231 

urea  the  diuretic  of,  vide  Diuretic 

urochromes  of,  10.  11,  119,  120,  125. 141, 
142,232 

watery  extracts  of,  54-56,  268 

xanthm  in,  231 
Urochromes,  intra-venous  injection  of,  53 

of  diabetes,  142,  247,  248 

of  dilated  stomach,  142, 165,  247 

of  dyspepsia,  141,  142,  247 

of  leucocytbaemia,  142,  247 

of  pyrexia,  240 

of  toxaemia,  142 

toxic  power  of,  vide  Toxic  power 

uraemia  due  to,  107,  119, 125 
Urotoxic  coefficient,  the,  35,  47 
Urticaria,  a  complication  of  hydatids,  162, 

in  dilated  stomach,  162,  163,  171 
toxic  origin  of,  162,  163 

Valeric  acid,  in  putrefactive  products,  93 
Variations  in  the  toxicity  of  urine,  34-46,  48 
Venesection,  in  anuria,  277 

in  uraemia,  133 
Vertigo,  in  constipation,  145 

in  dilated  stomach,  161 

in  dyspepsia,  140,  147 

in  toxaemia,  150 
Vicarious  functions,  19,  131 
Vomiting,  acid,  139 

exhaustion  due  to,  103 

in  intestinal  obstruction,  144 

in  toxaemia,  150 

in  uraemia,  108,  131 

uraemic  symptoms  due  to,  140 

Water,  disease  due  to,  10 

intra-venous  injections  of,  27,  75,  76,  111 

toxic  power  of,  10,  48,  75 
Watery  extracts,  intra-venous  injection 
of,  vide  Injections 

of  choleraic  urine,  268 

of  faeces.  94-96 

of  muscle,  79,  92,  93 

of  putrefactive  products,  91-93,  96 

of  urine,  54-56,  58 

Xanthin,  in  blood,  231 
in  urine,  231 
of  jaundice,  2S1 
toxic  power  of,  119 


I 

|={|  AUQUST,    1894. 

I 


Catalogue  of  the  Publications 


of 


THE  F.  A.  DAVIS  CO., 

JVIedieal     Publishers    and    Booksellers, 
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REFERENCE=  BOOKS  ANNOUNCED  IN 

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CATHELL— Book  on  the  Physician  Himself.     Page  2. 

DAVIS— Diseases  of  Lungs,  Heart,  and  Kidneys.    Page  2. 

EDINGER— The  Structure  of  the  Central  Nervous  System.    Page  3. 

EISENBERG— Bacteriological  Diagnosis.    Page  3. 

GOODELL— Lessons  in  Gynaecology.    Page  4. 

GRANDIN  and  JARflAN— Obstetric  Surgery.     Page  4. 

International  System  of  Electrotherapeutics.    Page  5. 

IVINS— Diseases  of  the  Nose  and  Throat.    Page  5. 

LIEBIG  and  ROHE— Electricity  in  riedicine  and  Surgery.    Page  6. 

riANTON— Syllabus  of  Lectures  on  Human  Embryology.    Page  6. 

PURDY— Practical  Uranalysis  and  Urinary  Diagnosis.    Page  8. 

ROHE— Text-Book  of  Hygiene.    Page  9. 

ROHE— Practical  flanual  of  Skin  Diseases.    Page  9. 

SENN— Principles  of  Surgery.     Page  9. 

SHOErtAKER— flateria  riedica  and  Therapeutics.    Page  10. 

SniTH— Physiology  of  the  Domestic  Animals.     Page  10. 

STEWART— Obstetric  Synopsis.     Page  11. 

YOUNG— Synopsis  of  Human  Anatomy.     Page  12. 

KRAFFT-EBING— Psychopathia  Sexualis.     Page  13. 

RANNEY— Lectures  on  Nervous  Diseases.     Page  13. 

SAJOUS— Lectures  on  Diseases  of  the  Nose  and  Throat.    Page  13. 

The  above  books  can  be  examined  and  obtained 
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Catalogue  of  the  Publications 

of 

THE  F.  A.  DAVIS  CO., 

Medical    Publishers    and    Booksellers, 

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*  BALLIN— Personal  Hygiene. 

By  MRS.  ADA  S.  BALLIN,  Editor  of  "Baby;  the  Mothers'  Magazine."  Crown 
Octavo.  About  250  pages.  Cloth. 

Price,  in  United  States  and  Canada,  6O  eta.,  net ;  Great  Britain, 
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BASHORE— Improved  Clinical  Chart. 

For  the  Separate  Plotting  of  Temperature,  Pulse,  and  Respiration.  Bat  one 
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BOENNINQ— Text-Book  on  Practical  Anatomy. 

Including  a  Section  on  Surgical  Anatomy.  By  HENRY  C.  BoEKNINO,  M.D., 
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Price,  in  United  States  and  Canada,  99.SO,  net;  Great  Britain.  14..; 
France,  16  fr.  2O. 

BOUCHARD— Auto-Intoxication. 

Being  a  series  of  lectures  on  Intestinal  and  Urinary  Pathology.  By  Prof.  CH. 
BOUCHARD,  Paris.  Translated  from  the  French,  with  un  Original  Appendix,  by 
THOMAS  OLIVER,  M.A.,  M.D.,  Professor  of  Physiology,  University  of  Durham. 
England.  Over  800  pages.  Crown  Octavo.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  91.75.  net;  Great  Britain,  !Os.j 
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BOWEN— Hand-Book  of  Materia  Medica,  Pharmacy,  etc. 

By  CUTHBERT  BOWEN,  M.D.,  B.A.    12mo.    370  pages.     Extra  Cloth. 
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Medical  Publications  of  The  F.  A.  Davis  Co.,  Philadelphia. 


BURET— Syphilis  in  Ancient  and  Prehistoric  Times. 

With  a  chapter  on  the  Rational  Treatment  of  Syphilis  in  the  Nineteenth  Cen- 
tury. By  Dr.  F.  BUKKT,  Paris,  France.  Translated  from  the  French,  with  the 
author's  permission,  with  notes,  by  A.  H.  OHMANN-DUMESNIL,  M.D.,  St.  Louis,  Mo. 
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Price,  in  United  States  and  Canada,  »1.25,  net ;  Great  Britain,  6s.  6d.; 
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CAPP— The  Daughter. 

Her  Health,  Education,  and  Wedlock.  Homely  Suggestions  to  Mothers  and 
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CATHELL— Book  on  the  Physician  Himself. 

And  Things  that  Concern  his  Reputation  and  Success.  By  D.  W.  CATHELL, 
M.D.,  Baltimore,  Md.  TENTH  EDITION.  Author's  last  revision.  Royal  Octavo. 
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CLEVENQER— Spinal  Concussion. 

Surgically  Considered  as  a  Cause  of  Spinal  Injury,  and  Neurologically  Re- 
stricted to  a  Certain  Symptom  Group,  for  which  is  Suggested  the  Designation  "Erich- 
sen's  Disease,"  as  one  form  of  the  Traumatic  Neuroses.  By  S.  V.  CLEVENQEB,  M.D., 
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COLTHAN— The  Chinese:  Their  Present  and  Future. 

Medical,  Political,  and  Social.  By  ROBERT  COLTMAN,  JR.,  M.D.,  Surgeon  in 
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Fine  Engravings  on  Extra  Plate  Paper,  from  photographs  of  persons,  places,  and 
objects  characteristic  of  China.  Royal  Octavo.  212  pages.  Extra  Cloth,  with 
Chinese  Side-Stamp  in  gold. 

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DAVIS— Diseases  of  the  Lungs,  Heart,  and  Kidneys. 

By  N.  S.  DAVIS.  JR.,  A.M.,  M.D.,  Professor  of  Principles  and  Practice  of 
Medicine,  Chicago  Medical  College,  etc.  12mo.  Over  800  pages.    Extra  Cloth. 
Price,  in  United  States  and  Canada,  JS1.25,  net ;  Great  Britain,  6s.  6d. ; 
France,  7  fr.  75. 
(2) 


Medical  Publications  of  The  F.  A.  Davis  Co.,  Philadelphia. 


DAVIS— Consumption :  How  to  Prevent  it  and  How  to 
Live  with  it. 

Its  Nature,  Causes,  Prevention,  and  the  Mode  of  Life,  Climate,  Exercise,  Food, 
and  Clothing  Necessary  for  its  Cure.  By  N.  S.  DAVIS,  JR.,  A.M.,  M.D.  12mo.  143 
pages.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  75  cts.,  net ;  Qreat  Britain,  4s. ; 
France,  4  fr. 

DEMARQUAY— On  Oxygen. 

A  Practical  Investigation  of  the  Clinical  and  Therapeutic  Value  of  the  Gases 
in  Medical  and  Surgical  Practice,  with  Especial  Reference  to  the  Value  and  Avail- 
ability of  Oxygen,  Nitrogen,  Hydrogen,  and  Nitrogen  Monoxide.  By  J.  N.  DEMAR- 
UUAY,  Surgeon  to  the  Municipal  Hospital,  Paris,  and  of  the  Council  of  State,  etc. 
Translated,  with  notes,  additions,  and  omissions,  by  s\ M  i >:i.  S.  WALLIAN,  A.M., 
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Octavo.  316  pages.  Illustrated  with  21  Wood-Cuts. 

Price,  in  United  States  and  Canada,  Cloth,  »2.OO,  net ;  Half-Russia.  U3.OO, 
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Cloth,  12  fr.  40 ;  Half-Russia,  18  fr.  GO. 

EDI NQER— Structure  of  the  Central  Nervous  System. 

For  Physicians  and  Students.  By  DR.  LUDWIG  EDINGKR,  Frank fort-on-the- 
Main.  Second  Revised  Edition.  With  1&3  illustrations.  Translated  by  WILLIS 
HALL  VITTOM,  M.D.,  St.  Paul,  Minn.  Edited  by  C.  EUGENIC  RIOGS,  A.M.,  M.D.. 
Professor  of  Mental  and  Nervous  Diseases,  University  of  Minnesota,  etc.  Royal 
Octavo.  About  250  pages.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  91.75,  net :  Great  Britain,  lOs. ; 
France,  12  fr.  2O. 

EISENBERQ— Bacteriological  Diagnosis. 

Tabular  Aids  for  use  in  Practical  Work.    By  JAMES  EISENBBRG,  Ph.D.,  M.D., 
Vienna.    Translated  and  augmented,  with  the  permission  of  the  author,  from  the 
second  German  Edition,  by  NORVAL  H.  PIERCE,  M.D.,  Chicago,  111.     Nearly  200 
pages.    Royal  Octavo,  bound  in  Cloth  and  in  Oil-Cloth  (for  laboratory  use). 
Price,  in  United  States  and  Canada,  Sl.AO,  net ;  Great  Britain,  HH.  <t<i. ; 
France,  9  fr.  35. 

FIREBAUGH—  The  Physician's  Wife. 

And  the  Things  that  Pertain  to  Her  Life.  By  KI.I.KN  M.  FiRKBACOH. 
Gracefully  written,  full  of  genuine  humor,  and  true  to  nature,  this  little  volume  la  a 
treasure  that  will  lighten  and  brighten  many  an  hour  of  care  and  worry.  Crown 
Ootavo,  200  pages,  with  44  Original  Character  Illustrations  and  a  Frontispiece  Por- 
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Special  Limited  Editions-First  500  copies  beautifully  printed  in  Photogra- 
vure Ink  on  Extra  <.jiialit>  KnaniHed  Paper,  with  wide  margins,  showing  the  illus- 
trations with  excellent  effect.  Beautifully  and  attractively  bound  in  Fine  Vollmu 
Cloth  and  Leather.  Price,  93.OO,  net.  The  Publishers  reserve  the  right  to  increase 
this  price  without  notioe. 

GANT  and  ALLINGHAM— Diseases  of  Rectum  and  Anus. 

By  S.  G.  GANT,  M.D.,  Professor  of  Rectal  and  Anal  Surgery  in  the  University 
Medical  College,  Kansas  City  ;  Lecturer  on  Rectal  and  Anal  Diseases  in  the  ScarriU 

(3) 


Medical  Publications  of  The  F.  A.  Davis  Co.,  Philadelphia. 


Training  School  and  Hospital  for  Nurses,  etc. ;  and  H.  W.  ALLINGHAM,  M.B. 
Surgeon  to  the  Great  Northern  Hospital,  and  Junior  Surgeon  to  St.  Mark's  Hospital 
for  Rectal  Diseases,  London,  etc.  With  numerous  Illustrations,  including  several 
Full-page  Colored  Photo-engravings.  Royal  Octavo.  IN  PREPARATION. 

GOODELL—  Lessons  in  Gynaecology. 

By  WILLIAM  GOODELL,  A.M.,  M.D.,  etc.,  Professor  of  Clinical  Gynaecology  in 
the  University  of  Pennsylvania.  With  112  Illustrations.  Third  Edition,  thoroughly 
revised  and  greatly  enlarged.  One  volume.  Large  Octavo.  578  pages. 

Price,  in  United  States  and  Canada,  Cloth,  S5.OO;  Full  Sheep,  S6.OO. 
Discount,  2O  per  cent.,  making  it,  net,  Cloth,  »4.OO ;  Sheep,  S4.8O. 
Postage,  27  cents  extra.  Great  Britain,  Cloth,  22s.  6d. ;  Sheep,  28s. 
France,  3O  fr.  80. 

QRANDIN  and  JARflAN— Obstetric  Surgery. 

By  EGBERT  H.  GRANDIN,  M.D.,  Obstetric  Surgeon  to  the  New  York  Maternity 
Hospital ;  Gynaecologist  to  the  French  Hospital,  etc. ;  and  GEORGE  W.  JARMAN, 
M.D.,  Obstetric  Surgeon  to  the  New  York  Maternity  Hospital ;  Gynaecologist  to  the 
Cancer  Hospital,  etc.  With  about  85  Illustrations  in  the  text  and  15  Full-page  Photo- 
graphic Plates.  Royal  Octavo.  About  250  pages.  Extra  Cloth. 

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GUERNSEY— Plain  Talks  on  Avoided  Subjects. 

By  HENRY  N.  GUERNSEY,  M.D.,  formerly  Professor  of  Materia  Medica  and 
Institutes  in  the  Hahnemann  Medical  College  of  Philadelphia,  etc.  Contents  of  the 
Book— I.  Introductory.  II.  The  Infant.  III.  Childhood.  IV.  Adolescence  of  the 
Male.  V.  Adolescence  of  the  Female.  VI.  Marriage :  The  Husband.  VII.  The 
Wife.  VIII.  Husband  and  Wife.  IX.  To  the  Unfortunate.  X.  Origin  of  the  Sex. 
liiino.  Bound  in  Extra  Cloth. 

Price,  in  the  United  States  and  Canada,  81.OO ;  Great  Britain,  6s. ; 
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HARE— Epilepsy :  Its  Pathology  and  Treatment. 

By  HOBART  AMORY  HARE,  M.D.,  B.Sc.,  Professor  of  Materia  Medica  and 
Therapeutics  in  the  Jefferson  Medical  College,  Philadelphia,  etc.  12mo.  228  pages. 
Extra  Cloth. 

Price,  in  United  States  and  Canada,  *1.25,  net ;  Great  Britain,  6s.  6d.  ; 
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HARE— Fever:  Its  Pathology  and  Treatment. 

Containing  Directions  and  the  Latest  Information  Concerning  the  Use  of  the 
So-called  Antipyretics  in  Fever  and  Pain.  By  HOBART  AMORY  HARE,  M.D.,  B.Sc. 
Illustrated  with  more  than  25  new  plates  of  tracings  of  various  fever  cases,  showing 
the  action  of  the  antipyretics.  The  work  also  contains  35  carefully-prepared  stalls. 
tical  tables  of  249  cases,  showing  the  untoward  effects  of  the  antipyretics.  12mo 
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HUIDEKOPER— Age  of  the  Domestic  Animals. 

Being  a  Complete  Treatise  on  the  Dentition  of  the  Horse,  Ox,  Sheep,  Hog,  and 
Dog,  and  on  the  various  other  means  of  determining  the  age  of  these  animals.  By 
RUSH  SHIPPEN  HUIDEKOPER,  M.D.,  Veterinarian  (Alfort,  France);  Professor  of 
Sanitary  Medicine  and  Veterinary  Jurisprudence,  American  Veterinary  College, 
New  York,  etc.  Royal  Octavo.  225  pages.  200  Wood-Engravings.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  91.75,  net;  Great  Britain,  lOs.; 
France  12  fr.  2O. 

International  System  of  Electro-Therapeutics. 

For  Students,  General  Practitioners,  and  Specialists.  Chief  Editor,  HORATIO 
R.  BIGELOW,  M.D.,  Fellow  of  the  American  Electro-Therapeutic  Association ; 
Member  of  the  Philadelphia  Obstetrical  Society ;  Member  of  the  Socidte  Fran- 
caise  d'Electro-The"rapie ;  Author  of  "Gynaecological  Electro-Therapeutics,"  and 
"  Familiar  Talks  on  Electricity  and  Batteries,"  etc.  Assisted  by  thirty-eight  eminent 
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many  fine  Engravings.  1160  pages.  Royal  Octavo. 

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IVINS— Diseases  of  the  Nose  and  Throat. 

A  Text-Book  for  Students  and  Practitioners.    By  HORACE  F.  IVINS,  M.D., 
Lecturer  on  Laryngology  and  Otology,  Hahnemann  Medical  College  of  Phila.,  etc. 
Royal  Octavo.     507  pages.     With  129   Illustrations,  chiefly  original,   including  18 
Colored  Figures  from  Drawings  and  Photographs  of  Anatomical  Dissections,  etc. 
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*  JOAL— On  Respiration  in  Singing. 

For  Specialists,  Singers,  Teachers,  Public  Speakers,  etc.  By  DR.  JOAL  (Mont 
Dore).  Translated  and  edited  by  R.  NOKRIS  WOI.FKNDKN,  M.IM'antah..  Kdltor  of 
the  Journal  of  Laryngology,  etc. ;  Vice-President  of  the  British  Laryngological 
Association,  etc.  IN  ACTIVE  PREPARATION.  NEARLY  READY.  Illustrated. 
Cloth.  Crown  Octavo.  Abont  240  pages. 

KEATING— Record-Book  of  Medical  Examinations  for  Life- 
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Designed  by  JOHN  M.  KEATING,  M.D.  This  record-book  Is  small,  but  com- 
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panies. It  is  made  in  two  siz.  s,  vi/  :  No.  1,  covering  one  hundred  (100)  examination*. 
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KEATING  and    EDWARDS— Diseases  of    the    Heart    and 
Circulation  in  Infancy  and  Adolescence. 

With  an  Appendix  entitled  "Clinical  Studies  on  the  Pulse  in  Childhood."  By 
JOHN  M.  KEATING,  M.D.,  Philadelphia,  and  WILLIAM  A.  EDWARDS,  M.D.,  Phila- 
delphia. Illustrated  by  Photographs  and  Wood-Engravings.  About  225  pages.  8vo. 
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KRAFFT-EBINQ— A  Text-Book  on  Insanity. 

For  the  Use  of  Students  and  Practitioners.  By  Dr.  R.  VON  KRAFFT-EBING. 
Authorized  translation  of  the  Fifth  German  Edition  by  CHARLES  GILBERT  CHAD- 
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Medicine,  St.  Louis,  Mo.,  etc.  Royal  Octavo.  About  800  pages.  IN  PREPARATION. 

LIEBIQ  and  ROME— Electricity  in  Medicine  and  Surgery. 

By  G.  A.  LIEBIG,  Jr.,  Ph.D.,  Assistant  in  Electricity,  Johns  Hopkins  Uni- 
versity, etc. ;  and  GEORGE  H.  ROHE,  M.D.,  Professor  of  Obstetrics  and  Hygiene, 
College  of  Physicians  and  Surgeons,  Baltimore.  Profusely  Illustrated  by  Wood- 
Engravings  and  Original  Diagrams.  Royal  Octavo.  383  pages.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  S2.OO,  net;  Great  Britain,  lls.  6d. ; 
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flANTON — A  Syllabus  of  Lectures  on  Human  Embryology. 

An  Introduction  to  the  Study  of  Obstetrics  and  Gynaecology,  with  a  Glossary 
of  Embryological  Terms.  By  WALTER  PORTER  MANTON,  M.D.,  Lecturer  on  Ob- 
stetrics in  Detroit  College  of  Medicine ;  Fellow  of  the  Royal  Microscopical  Society, 
of  the  British  Zoological  Society,  etc.  Interleaved  for  taking  notes,  and  thoroughly 
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pages,  besides  the  blank  leaves  for  notes.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  SH.25,  net ;  Great  Britain,  6s.  6d. ; 
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MASSEY— Electricity  in  the  Diseases  of  Women. 

With  Special  Reference  to  the  Application  of  Strong  Currents.  By  G.  BETTON 
MASSEY,  M.D.,  Late  Electro-Therapeutist  to  the  Philadelphia  Orthopaedic  Hospital 
and  Infirmary  for  Nervous  Diseases,  etc.  Second  Edition.  Revised  and  Enlarged. 
With  New  and  Original  Wood-Engravings.  Extra  Cloth.  240  pages.  12mo. 

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Hedical  Bulletin  Visiting  List,  or  Physicians'  Call  Record. 

Arranged  upon  an  Original  and  Convenient  Monthly  and  Weekly  Plan  for  the 
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Medical  Publications  of  the  F.  A.  Davis  Co ,  Philadelphia. 


niCHENER— Hand-Book  of  Eclampsia. 

Or,  Notes  and  Cases  of  Puerperal  Convulsions.  By  E.  MICIIENER,  M.D. ; 
.1.  H.  STUBBS,  M.D.  ;  K.  B.  EWING,  M.D. ;  B.  THOMPSON,  M.D. ;  8.  STEBBINS, 
M.D.  16mo.  Cloth.  Price,  6O  cts.,  net.  Great  Britain,  3s.  6d. 

nONTGOMERY— Practical  Gynaecology. 

By  E.  E.  MONTGOMERY,  A.M.,  M.D.,  Professor  of  Clinical  Gynaecology  in  the 
Jefferson  Medical  College,  Philadelphia,  etc.,  etc.  In  one  Royal  Octavo  volume. 
Thoroughly  Illustrated.  IN  PREPARATION. 

*MOORE— fleteorology. 

By  J.  W.  MOORE,  B.A.,  M.Ch.,  University  of  Dublin  ;  Fellow  and  Registrar  of 
the  Royal  College  of  Physicians  of  Ireland,  etc.  Part  I.  Physical  Properties  of  the 
Atmosphere.  Part  II.  A  Complete  History  of  the  United  States  Weather  Bureau 
from  its  Beginning  to  the  Present  Day,  specially  contributed  by  Prof.  W.  M. 
HARRINGTON,  Chief  of  the  Weather  Bureau  in  Washington,  D.C.,  giving  also  a  full 
list  of  all  the  stations  under  the  immediate  control  of  the  United  States  Government. 
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pages.  Cloth. 

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*MYGIND— Deaf-Mutism. 

By  HOLQER  MYGIND,  M.D.,  of  Copenhagen.  The  only  authorized  English 
Edition.  Comprising  Introduction,  Etiology  and  Patho^cni-sis,  Morbid  Anatomy, 
Symptoms  and  Sequelae,  Diagnosis,  Prognosis,  and  Treatment.  Crown  Octavo. 
About  300  pages.  Cloth. 

Price,  post-paid,  in  United  States  and  Canada,  92. OO,  net;  Great 
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NISSEN— A   Manual   of    Instruction   for    Giving    Swedish 
flovement  and  Massage  Treatment. 

By  Prof.  HARTVIG  NISSEN,  late  Instructor  in  Physical  Culture  and  Gym- 
nastics at  the  Johns  Hopkins  University,  Baltimore,  Md.,  etc.  With  29  Original 
Wood-Engravings.  12mo.  128  pages.  Cloth. 

Price,  in  United  States  and  Canada,  Wl.oo,  net ;  Great  Britain,  6». ; 
France,  6  fr.  2O. 

Physicians'     All-Requisite     Time-    and     Labor-    Saving 
Account-Book. 

B«>ing  a  ledger  and  Account-Book  for  Physician*'  I'sr.  mot-ting  all  tli.  !:•• 
quirements  of  the  IAW  and  Court*.  Designed  by  WILLIAM  A.  SKIHKKT.  Ml).,  of 
Huston,  Pa.  There  is  no  exaggeration  in  stating  that  this  Account-Book  and  I^-.lcor 
reduces  the  labor  of  keeping  physicians'  accounts  more  than  one-half,  and  at  tli« 
saint-  time  secures  the  greatest  degree  of  accuracy. 

Prices :  No.  1,  300  pages  for  900  Accounts  per  Year,  sizn  10  x  12,  bound 
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Medical  Publications  of  The  F.  A.  Davis  Co.,  Philadelphia. 


Physicians'  Interpreter. 

In  Four  Languages,  English,  French,  German,  and  Italian.    Specially  arranged 

for  diagnosis  by  M.  VON  V.     The  plan  of  the  book  is  a  systematic  arrangement  of 

questions  upon  the  various  branches  of  Practical  Medicine,  and  each  question  is  so 

worded  that  the  only  answer  required  of  the  patient  is  merely  Yes  or  No.    Bound  In 

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PURDY— Diabetes. 

Its  Cause,  Symptoms,  and  Treatment.  By  CHAS.  W.  PURDY,  M.D.,  Honorary 
Fellow  of  the  Royal  College  of  Physicians  and  Surgeons  of  Kingston ;  Author  of 
"Bright's  Disease  and  Allied  Affections  of  the  Kidneys"  ;  Member  of  the  Associa- 
tion of  American  Physicians ;  Member  of  the  American  Medical  Association,  etc., 
etc.  With  Clinical  Illustrations.  12mo.  184  pages.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  SI. 25,  net ;  Great  Britain,  6s.  6d. ; 
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PURDY— Practical  Uranalysis  and  Urinary  Diagnosis. 

A  Manual  for  the  Use  of  Physicians  and  Students.     By  CHAS.  W.  PURDY, 
M.D.,  Author  of  "  Diabetes :  its  Cause,  Symptoms,  and  Treatment ";  Member  of  the 
Association  of  American  Physicians,  etc.,  etc.    With  numerous  Illustrations,  includ- 
ing several  Colored  Plates.    Crown  Octavo.    About  350  pages.    Extra  Cloth. 
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REflONDINO— History  of  Circumcision. 

From  the  Earliest  Times  to  the  Present.  Moral  and  Physical  Reasons  for  its 
Performance ;  with  a  History  of  Eunuchism,  Hermaphrodism,  etc.,  and  of  the 
Different  Operations  Practiced  upon  the  Prepuce.  By  P.  C.  REMONDINO,  M.D., 
Member  of  the  American  Medical  Association,  of  the  American  Public  Health 
Association  ;  Vice-President  of  California  State  Medical  Society,  etc.  12mo.  346 
pages.  Extra  Cloth.  Illustrated  with  two  fine  full-page  Wood-Engravings,  showing 
the  two  principal  modes  of  Circumcision  in  ancient  times. 

Price,  in  United  States  and  Canada,  S1.25,  net;  Great  Britain,  6s.  6d.; 
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France,  3  fr.  6O. 

REflONDINO— The  flediterranean  Shores  of  America. 

Southern  California:  its  Climatic,  Physical,  and  Meteorological  Conditions. 
By  P.  C.  REMONDINO,  M.D.  Royal  Octavo.  175  pages.  With  45  appropriate  Illus- 
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etc.  Bound  in  Extra  Cloth. 

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*ROBINSON  and  CRIBB— The  Law  and  Chemistry  Relating 
to  Food. 

A  Manual  for  the  Use  of  persons  practically  interested  in  the  Administration 
of  the  Law  relating  to  the  Adulteration  and  Unsoundness  of  Food  and  Di  ugs.    By  H. 
MANSFIELD  ROBINSON,  LL.D.  (London),  Solicitor  and  Clerk  to  the  Shoreditch 
(8) 


Medical  Publications  of  The  F.  A.  Dan's  Co.,  Philadelphia. 


Sanitary  Authority  ;•  Law  Examiner  for  the  British  Institute  of  Public  Healtk, 
etc. ;  and  CECIL  H.  CRIBB,  B.Sc.  (London),  F.I.C.,  F.C.S.,  Public  Analyst  to  the 
Strand  District,  etc.  Crown  Octavo.  About  300  pages. 

Price,  in  United  States  and  Canada,  92.OO,  net ;  Great  Britain,  8s. ; 
France,  9  fr.  5O. 

ROME— Text-Book  of  Hygiene. 

A  Comprehensive  Treatise  on  the  Principles  and  Practice  of  Preventive  Medi- 
cine from  an  American  Stand-point.  By  GEORGE  H.  ROHE,  M.D.,  Professor  of  Ob- 
stetrics and  Hygiene  in  the  College  of  Physicians  and  Surgeons,  Baltimore  ;  Member 
of  the  American  Public  Health  Association,  etc.  THIRD  EDITION,  carefully 
revised  and  enlarged,  with  many  Illustrations  and  valuable  Tables.  Royal  Octavo. 
Over  450  pages.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  «3.OO,  net ;  Great  Britain,  14s. ; 
France,  18  fr.  6O. 

ROHE— A  Practical  flanual  of  Diseases  of  the  Skin. 

By  GEORGE  H.  ROHE,  M.D.,  assisted  by  J.  WILLIAMS  LORD,  A.B.,  M.D.,  Lect- 
urer on  Dermatology  and  Bandaging  in  the  College  of  Physicians  and  Surgeons, 
Baltimore,  etc.  12mo.  Over  300  pages.  Extra  Cloth. 

Price,  in  United  States  and  Canada,  91.95,  net ;  Great  Britain,  6s.  6d. ; 
France,  7  fr.  75. 

SAJOUS — Hay  Fever  and  its  Successful  Treatment, 

BY  SUPERFICIAL  ORGANIC  ALTERATION  OF  THE  NASAL  Mucous  MEM- 
BRANE.     By  CHARLES  E.  SAJOUS,  M.D.,  Chief  Editor  "Annual  of  the  Universal 
Medical  Sciences"  ;  formerly  Lecturer  on  Rhinology  and  Laryngology  in  the  Jeffer- 
son Medical  College,  etc.    With  13  Engravings  on  Wood.    12mo.    Extra  Cloth. 
Price,  in  United  States  and  Canada,  91.OO,  net;  Great  Britain,  6s. ; 
France,  6  fr.  2O. 

*  SCHUSTER— When  is  flarriage  Permissible  after  Syphilis? 

By  DR.  SCHUSTER,  of  Aix-la-Chapelle.  Translated  from  the  German  by  C. 
RENNER,  M.D.,  London.  8vo.  32  pages.  Price,  25  cents  net,  or  1  shilling. 

SENN— Principles  of  Surgery. 

By  N.  SKNN,  M.D.,  Ph.D.,  Professor  of  Principles  of  Surgery  and  Surgical 
Pathology  in  Rush  Medical  College,  Chicago,  III. ;  Professor  of  Surgery  in  the 
Chicago  Polyclinic,  etc.    Royal  Octavo.    With  109  fine  Wood-Engravings.   824  pages. 
Price,  in  United  States  and  Canada,  Cloth,  94.5O,  not;  Sheep  or  Half- 
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Russia,    SOs.      France,    Cloth,    27   fr.  2O ;  Sheep  or    Half-Russia, 
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SENN— Tuberculosis  of  the  Bones  and  Joints. 

By  N.  SKNN,  M.D.,  Ph.D.,  author  of  a  text-book  on  the  "Principles  of  Sur- 
gery," etc.  Royal  Octavo.  Over  500  pages.  Illustrated  with  107  Engravings,  many 
of  them  colored. 

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SHOEMAKER— Heredity,  Health,  and  Personal  Beauty. 

Including  the  Selection  of  the  Best  Cosmetics  for  the  Skin,  Hair,  Nails,  and 
All  Parts  Relating  to  the  Body.  By  JOHN  V.  SHOEMAKER,  A.M.,  M.D.,  Professor' 
of  Materia  Medica,  Pharmacology,  Therapeutics,  and  Clinical  Medicine,  and  Clini- 
cal Professor  of  Diseases  of  the  Skin  in  the  Medico-Chirurgical  College  of  Philadel- 
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(14) 


Date  Due 


I! 


A  000  498  886 


QZUO 

B752L 

189U 

Bouchard,  Charles. 

Lectures  on  auto-intoxication  in 
disease. 


QZl*0 


uchard,  Charles. 

Lectures  on  auto-intoxication  in 
Dsease. 


MEDICAL  SCIENCES  LIBRARY 

UNIVERSITY  OF  CALIFORNIA,  IRVINE 

IRVINE,  CALIFORNIA  92664 


